Is ABCC5 p.Arg251Gln (c.752G>A) pathogenic?

ABCC5 p.Arg251Gln (c.752G>A) is classified Uncertain significance in ABCC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: ambiguous (0.4393); Very rare (popmax 0.005%, amr).

How common is ABCC5 p.Arg251Gln (c.752G>A) in the general population?

ABCC5 p.Arg251Gln (c.752G>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ABCC5 p.Arg251Gln (c.752G>A)?

AlphaMissense predicts ambiguous (score 0.4393) — an in-silico prediction, not a clinical call.

ABCC5 p.Arg251Gln

c.752G>A · rs767886323 · VCV2259426

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4393 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4393	ambiguous
REVEL	0.895	moderately pathogenic-leaning
SaProt	LLR -10.45	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 72 kb · p 6.6e-23 · regional, not allelic
Overall
CADD	32.0	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 0.005% Admixed American · 3/60,018 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000821% 12/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,006
East Asian	0.00223%	44,884
European (non-Finnish)	0.000678%	147,505

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: ABCC5
Protein: p.Arg251Gln
Coding: c.752G>A
MANE Select: NM_005688
dbSNP: rs767886323
Type: single nucleotide variant
Location: chr3:183982847 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.13 · 6 PDB
Residue 251: the abc transmembrane type-1 1 domain; an α-helix

Full ABCC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC5 c.825+10G>A Benign ★★ same type
ABCC5 p.Cys594= Benign ★★ same type
ABCC5 p.Ala1008Ser Uncertain significance ★ ⚠ same type
ABCC5 p.Ala1150Thr Uncertain significance ★ ⚠ same type
ABCC5 p.Ala1182Val Uncertain significance ★ ⚠ same type
ABCC5 p.Ala1302Gly Uncertain significance ★ ⚠ same type
ABCC5 p.Ala1343Thr Uncertain significance ★ ⚠ same type
ABCC5 p.Ala1434Thr Uncertain significance ★ ⚠ 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/abcc5-p-arg251gln (accessed [today's date]).

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