Is ABCA4 p.Phe191Ile (c.571T>A) pathogenic?

ABCA4 p.Phe191Ile (c.571T>A) is classified Uncertain significance in ABCA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-31). AlphaMissense: ambiguous (0.4586); Ultra-rare (popmax 0.0147%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABCA4 p.Phe191Ile (c.571T>A)?

ABCA4 p.Phe191Ile (c.571T>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABCA4 p.Phe191Ile (c.571T>A) in the general population?

ABCA4 p.Phe191Ile (c.571T>A) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about ABCA4 p.Phe191Ile (c.571T>A)?

AlphaMissense predicts ambiguous (score 0.4586) — an in-silico prediction, not a clinical call.

ABCA4 p.Phe191Ile

c.571T>A · rs200696846 · VCV1042537

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4586 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4586	ambiguous
REVEL	0.531	indeterminate
SaProt	LLR -7.32	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	23.6	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 0.0147% African / African-American · 11/75,030 alleles

Filtering AF 0.00814% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000934% 15/1,605,408 alleles · ultra-rare exomes 7/1,453,098 · genomes 8/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,821
Remaining individualsnot grpmax-eligible	0.0016%	62,376
European (non-Finnish)	0.000254%	393,191

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.Phe191Ile
Coding: c.571T>A
MANE Select: NM_000350
dbSNP: rs200696846
Type: single nucleotide variant
Location: chr1:94098991 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 191: a UniProt-annotated variant site (in cord3; uncertain significance); a UniProt-annotated variant site (in stgd1; uncertain significance)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA4 p.Phe191= Conflicting classifications of pathogenicity ★ same residue
ABCA4 p.Ala1287Val Uncertain significance ★★ ⚠ same condition
ABCA4 p.Ala1324Val Uncertain significance ★★ ⚠ same condition
ABCA4 p.Ala45Gly Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg1170Thr Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg140Pro Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg1963His Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg487Pro Uncertain significance ★★ ⚠ 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-phe191ile (accessed [today's date]).

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