Is ABCA4 p.Pro327= (c.981C>T) pathogenic?

ABCA4 p.Pro327= (c.981C>T) is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-01-11). Ultra-rare (popmax 0.0986%, mid); Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Pro327= (c.981C>T)?

ABCA4 p.Pro327= (c.981C>T) is associated with ABCA4-related disorder, inherited retinal dystrophy (ClinVar).

How common is ABCA4 p.Pro327= (c.981C>T) in the general population?

ABCA4 p.Pro327= (c.981C>T) is ultra-rare (popmax 0.0986%, mid) (gnomAD).

ABCA4 p.Pro327=

c.981C>T · rs61753057 · VCV99516

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0986%, mid)

Conditions

ABCA4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.59	phastCons 0.066
Overall
CADD	6.973	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0986% Middle Eastern · 6/6,084 alleles

Filtering AF 0.0751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0734%

Overall 0.0662% 1,069/1,613,902 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0986%	1,014
European (non-Finnish)	0.0793%	1,261
South Asian	0.0725%	1,380
Remaining individualsnot grpmax-eligible	0.0448%	2,232
African / African-American	0.0187%	5,346
East Asian	0.0156%	6,409
Admixed American	0.0117%	8,569
Finnishnot grpmax-eligible	0.00781%	12,802

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.Pro327=
Coding: c.981C>T
MANE Select: NM_000350
dbSNP: rs61753057
Type: single nucleotide variant
Location: chr1:94080596 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 327: 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)

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

Disease context

Also linked: inherited retinal dystrophy

Similar variants

ABCA4 c.1937+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
ABCA4 c.4773+3A>G Pathogenic ★★★ same condition
ABCA4 c.5018+2T>A Pathogenic ★★★ same condition
ABCA4 c.5018+2T>C Pathogenic ★★★ same condition
ABCA4 c.5196+1137G>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-pro327 (accessed [today's date]).

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