Is ABCA13 p.Arg4863Gln (c.14588G>A) pathogenic?

ABCA13 p.Arg4863Gln (c.14588G>A) is classified Uncertain significance in ABCA13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: ambiguous (0.4822); Ultra-rare (popmax 0.0172%, nfe).

How common is ABCA13 p.Arg4863Gln (c.14588G>A) in the general population?

ABCA13 p.Arg4863Gln (c.14588G>A) is ultra-rare (popmax 0.0172%, nfe) (gnomAD).

What do computational predictors say about ABCA13 p.Arg4863Gln (c.14588G>A)?

AlphaMissense predicts ambiguous (score 0.4822) — an in-silico prediction, not a clinical call.

ABCA13 p.Arg4863Gln

c.14588G>A · VCV3503506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4822 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0172%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4822	ambiguous
REVEL	0.588	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 258 kb · p 0.16 · regional, not allelic
Overall
CADD	31.0	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 0.0172% European (non-Finnish) · 203/1,179,106 alleles

Filtering AF 0.0152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0145%

Overall 0.013% 210/1,612,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0172%	5,808
Remaining individualsnot grpmax-eligible	0.00641%	15,598
East Asian	0.00223%	44,784
African / African-American	0.00134%	74,896
South Asian	0.0011%	90,576

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: ABCA13
Protein: p.Arg4863Gln
Coding: c.14588G>A
MANE Select: NM_152701
Type: single nucleotide variant
Location: chr7:48587236 (GRCh38)
Gene constraint: LOEUF 1.063 · pLI <0.01 (gnomAD)
Residue 4863: the abc transporter 2 domain

Full ABCA13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA13 p.Arg4863Trp Uncertain significance ★ same residue
ABCA13 p.Ala1627Val Uncertain significance ★★ ⚠ same type
ABCA13 p.Ala4240Thr Uncertain significance ★★ ⚠ same type
ABCA13 c.1263-5C>G Benign/Likely benign ★★ same type
ABCA13 p.Ala2178Glu Benign ★★ same type
ABCA13 p.Ala922Thr Benign ★★ same type
ABCA13 p.Arg4043Cys Benign ★★ same type
ABCA13 p.Arg4070Cys Benign ★★ 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/abca13-p-arg4863gln (accessed [today's date]).

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