Is CCAR1 p.Asp985Ala (c.2954A>C) pathogenic?

CCAR1 p.Asp985Ala (c.2954A>C) is classified Uncertain significance in CCAR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.2255); Ultra-rare (popmax 0.0143%, sas).

How common is CCAR1 p.Asp985Ala (c.2954A>C) in the general population?

CCAR1 p.Asp985Ala (c.2954A>C) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

What do computational predictors say about CCAR1 p.Asp985Ala (c.2954A>C)?

AlphaMissense predicts likely benign (score 0.2255) — an in-silico prediction, not a clinical call.

CCAR1 p.Asp985Ala

c.2954A>C · rs761752782 · VCV2210291

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2255 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2255	likely benign
REVEL	0.464	indeterminate
SaProt	LLR -7.06	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 20 kb · p 0.016 · regional, not allelic
Overall
CADD	27.2	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 0.0143% South Asian · 13/90,906 alleles

Filtering AF 0.00846% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00676%

Overall 0.00719% 116/1,612,902 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	6,993
European (non-Finnish)	0.00865%	11,562
Remaining individualsnot grpmax-eligible	0.0016%	62,442

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: CCAR1
Protein: p.Asp985Ala
Coding: c.2954A>C
MANE Select: NM_018237
dbSNP: rs761752782
Type: single nucleotide variant
Location: chr10:68788000 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.55
Residue 985: the 'interaction with gata1' region

Full CCAR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCAR1 c.1625+1G>A Uncertain significance ★ same type
CCAR1 p.Ala2Val Uncertain significance ★ ⚠ same type
CCAR1 p.Ala499Asp Uncertain significance ★ ⚠ same type
CCAR1 p.Ala878Ser Uncertain significance ★ ⚠ same type
CCAR1 p.Arg300Gln Uncertain significance ★ ⚠ same type
CCAR1 p.Arg307Thr Uncertain significance ★ ⚠ same type
CCAR1 p.Arg327His Uncertain significance ★ ⚠ same type
CCAR1 p.Arg340Leu 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/ccar1-p-asp985ala (accessed [today's date]).

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