Is ABCA4 p.Val598Met (c.1792G>A) pathogenic?

ABCA4 p.Val598Met (c.1792G>A) is classified Uncertain significance in ABCA4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-07-27). AlphaMissense: likely benign (0.0916); Ultra-rare (popmax 0.0297%, nfe); Associated with cone-rod dystrophy 3.

What condition is associated with ABCA4 p.Val598Met (c.1792G>A)?

ABCA4 p.Val598Met (c.1792G>A) is associated with cone-rod dystrophy 3, age related macular degeneration 2, severe early-childhood-onset retinal dystrophy (ClinVar).

How common is ABCA4 p.Val598Met (c.1792G>A) in the general population?

ABCA4 p.Val598Met (c.1792G>A) is ultra-rare (popmax 0.0297%, nfe) (gnomAD).

How is Cone rod dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABCA4 p.Val598Met (c.1792G>A)?

AlphaMissense predicts likely benign (score 0.0916) — an in-silico prediction, not a clinical call.

ABCA4 p.Val598Met

c.1792G>A · rs201838557 · VCV849480

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0916 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0297%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cone-rod dystrophy 3

Computational evidence

Protein change
AlphaMissense	0.0916	likely benign
REVEL	0.376	indeterminate
SaProt	LLR -6.19	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -3, phastCons 0.99
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	19.78	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0297% European (non-Finnish) · 350/1,180,016 alleles

Filtering AF 0.0271% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0261%

Overall 0.0234% 378/1,613,942 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0297%	3,371
Remaining individualsnot grpmax-eligible	0.0288%	3,472
African / African-American	0.00801%	12,483
Finnishnot grpmax-eligible	0.00312%	32,003
East Asian	0.00223%	44,884
Admixed American	0.00167%	59,986

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCA4
Protein: p.Val598Met
Coding: c.1792G>A
MANE Select: NM_000350
dbSNP: rs201838557
Type: single nucleotide variant
Location: chr1:94062722 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 598: a UniProt-annotated variant site (in cord3; uncertain significance); a UniProt-annotated variant site (in stgd1; uncertain significance); a UniProt-annotated variant site (found in a patient with chorioretinal atrophy; uncertain significance); a turn

Full ABCA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cone-rod dystrophy 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: age related macular degeneration 2 severe early-childhood-onset retinal dystrophy retinitis pigmentosa 19 inherited retinal dystrophy ABCA4-related retinopathy

For Cone rod dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

ABCA4 p.Val598Gly Uncertain significance ★ ⚠ same residue
ABCA4 p.Val598= Likely benign ★ same residue
ABCA4 c.1937+1G>A Pathogenic ★★★ same condition
ABCA4 c.3328+2T>A Pathogenic ★★★ same condition
ABCA4 c.3523-1G>A Pathogenic ★★★ same condition
ABCA4 c.4253+43G>A Pathogenic ★★★ same condition
ABCA4 c.4254-1G>C Pathogenic ★★★ same condition
ABCA4 c.4352+1G>A Pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abca4-p-val598met (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown