Is ABCC5 p.Arg168Gln (c.503G>A) pathogenic?

ABCC5 p.Arg168Gln (c.503G>A) is classified Uncertain significance in ABCC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-22). AlphaMissense: likely benign (0.0891); Very rare (popmax 0.00127%, nfe).

How common is ABCC5 p.Arg168Gln (c.503G>A) in the general population?

ABCC5 p.Arg168Gln (c.503G>A) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about ABCC5 p.Arg168Gln (c.503G>A)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

ABCC5 p.Arg168Gln

c.503G>A · rs749531253 · VCV2603605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 72 kb · p 6.6e-23 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% European (non-Finnish) · 15/1,180,022 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00109% 16/1,461,868 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00127%	78,668
South Asian	0.0011%	91,084

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.Arg168Gln
Coding: c.503G>A
MANE Select: NM_005688
dbSNP: rs749531253
Type: single nucleotide variant
Location: chr3:183987858 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.13 · 6 PDB
Residue 168: an α-helix

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

Similar variants

ABCC5 p.Arg168Pro Uncertain significance ★ ⚠ same residue
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

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-arg168gln (accessed [today's date]).

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