Is ABCA4 p.Gln110Pro (c.329A>C) pathogenic?

ABCA4 p.Gln110Pro (c.329A>C) is classified Likely pathogenic in ABCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-03). AlphaMissense: likely benign (0.2231); Absent from gnomAD v4.1.

How common is ABCA4 p.Gln110Pro (c.329A>C) in the general population?

ABCA4 p.Gln110Pro (c.329A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCA4 p.Gln110Pro (c.329A>C)?

AlphaMissense predicts likely benign (score 0.2231) — an in-silico prediction, not a clinical call.

ABCA4 p.Gln110Pro

c.329A>C · rs2101156046 · VCV1513023

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2231 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2231	likely benign ⚠ discordant with ClinVar
REVEL	0.852	moderately pathogenic-leaning
SaProt	LLR -10.14	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -3.2, phastCons 0.92
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	19.94	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCA4
Protein: p.Gln110Pro
Coding: c.329A>C
MANE Select: NM_000350
dbSNP: rs2101156046
Type: single nucleotide variant
Location: chr1:94108690 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 110: a UniProt-annotated variant site (in cord3; uncertain significance); an α-helix; a disulfide bond; a UniProt-annotated variant site (in stgd1; uncertain significance)

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

Similar variants

ABCA4 p.Gln110Ter Pathogenic/Likely pathogenic ★★ same residue
ABCA4 p.Gln110delinsXaaXaaXaaXaaLysLysLysLys Pathogenic ★ same residue
ABCA4 p.Gln110fs Pathogenic same residue
ABCA4 c.1937+1G>A Pathogenic ★★★ same type
ABCA4 c.3328+2T>A Pathogenic ★★★ same type
ABCA4 c.3523-1G>A Pathogenic ★★★ same type
ABCA4 c.4253+43G>A Pathogenic ★★★ same type
ABCA4 c.4254-1G>C Pathogenic ★★★ same type

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-gln110pro (accessed [today's date]).

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