Is ABCA4 p.Phe873Leu (c.2617T>C) pathogenic?

ABCA4 p.Phe873Leu (c.2617T>C) is classified Pathogenic in ABCA4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-16). AlphaMissense: likely pathogenic (0.9117); Very rare (popmax 0.00136%, nfe); Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Phe873Leu (c.2617T>C)?

ABCA4 p.Phe873Leu (c.2617T>C) is associated with ABCA4-related disorder, retinitis pigmentosa (ClinVar).

How common is ABCA4 p.Phe873Leu (c.2617T>C) in the general population?

ABCA4 p.Phe873Leu (c.2617T>C) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about ABCA4 p.Phe873Leu (c.2617T>C)?

AlphaMissense predicts likely pathogenic (score 0.9117) — an in-silico prediction, not a clinical call.

ABCA4 p.Phe873Leu

c.2617T>C · rs62642570 · VCV99149

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9117 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCA4-related disorder

Computational evidence

Protein change
AlphaMissense	0.9117	likely pathogenic ✓ concordant with ClinVar · top 8% in ABCA4
REVEL	0.962	strongly pathogenic-leaning
SaProt	LLR -12.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,179,912 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00116% 17/1,461,730 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,048
European (non-Finnish)grpmax	0.00136%	73,745

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe873Leu
Coding: c.2617T>C
MANE Select: NM_000350
dbSNP: rs62642570
Type: single nucleotide variant
Location: chr1:94051669 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 873: 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 UniProt-annotated variant site (found in a patient with macular dystrophy; uncertain significance); a UniProt-annotated variant site (in stgd1); a turn; a disulfide bond

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

Disease context

Also linked: retinitis pigmentosa

Similar variants

ABCA4 c.5460+1G>A Pathogenic ★★★ same condition
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ABCA4 p.Ala967Val Likely pathogenic ★★★ ⚠ same condition
ABCA4 p.Arg2139Trp Pathogenic ★★★ same condition
ABCA4 p.Arg408Ter Pathogenic ★★★ same condition
ABCA4 p.Arg572Pro Pathogenic ★★★ same condition
ABCA4 p.Arg602Trp Pathogenic ★★★ ⚠ same condition
ABCA4 p.Asn965Ser 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-phe873leu (accessed [today's date]).

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