Is CCAR1 p.Arg971His (c.2912G>A) pathogenic?

CCAR1 p.Arg971His (c.2912G>A) is classified Uncertain significance in CCAR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely pathogenic (0.7707); Very rare (popmax 0.00668%, afr).

How common is CCAR1 p.Arg971His (c.2912G>A) in the general population?

CCAR1 p.Arg971His (c.2912G>A) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about CCAR1 p.Arg971His (c.2912G>A)?

AlphaMissense predicts likely pathogenic (score 0.7707) — an in-silico prediction, not a clinical call.

CCAR1 p.Arg971His

c.2912G>A · VCV4220194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7707 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7707	likely pathogenic
REVEL	0.14	moderately benign-leaning
SaProt	LLR -8.56	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.88, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 20 kb · p 0.016 · regional, not allelic
Overall
CADD	25.9	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 0.00668% African / African-American · 5/74,836 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00192% 31/1,612,592 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,967
Remaining individualsnot grpmax-eligible	0.00641%	15,605
Admixed American	0.00502%	19,925
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,588
European (non-Finnish)	0.00144%	69,375
South Asian	0.0011%	90,800

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.Arg971His
Coding: c.2912G>A
MANE Select: NM_018237
Type: single nucleotide variant
Location: chr10:68787958 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.55
Residue 971: 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-arg971his (accessed [today's date]).

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