Is CCAR2 p.Thr461Met (c.1382C>T) pathogenic?

CCAR2 p.Thr461Met (c.1382C>T) is classified Likely benign in CCAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-05). AlphaMissense: likely benign (0.0777); Ultra-rare (popmax 0.0111%, eas).

How common is CCAR2 p.Thr461Met (c.1382C>T) in the general population?

CCAR2 p.Thr461Met (c.1382C>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about CCAR2 p.Thr461Met (c.1382C>T)?

AlphaMissense predicts likely benign (score 0.0777) — an in-silico prediction, not a clinical call.

CCAR2 p.Thr461Met

c.1382C>T · rs372863532 · VCV2590929

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0777 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0777	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -8.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.61	GERP -3, phastCons 0.001
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.54 · regional, not allelic
Overall
CADD	7.994	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 0.0111% East Asian · 5/44,884 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00378% 61/1,613,578 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,977
South Asian	0.011%	9,108
Remaining individualsnot grpmax-eligible	0.0096%	10,413
African / African-American	0.00534%	18,716
European (non-Finnish)	0.00305%	32,778

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: CCAR2
Protein: p.Thr461Met
Coding: c.1382C>T
MANE Select: NM_001393997
dbSNP: rs372863532
Type: single nucleotide variant
Location: chr8:22615686 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.61 · 1 PDB
Residue 461: the 'disordered' region

Full CCAR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCAR2 p.Ala388= Benign ★★ same type
CCAR2 p.Ala794= Benign ★★ same type
CCAR2 p.Arg336= Likely benign ★★ same type
CCAR2 c.1990+1G>T Uncertain significance ★ same type
CCAR2 c.2521+1G>A Uncertain significance ★ same type
CCAR2 c.927+38G>C Uncertain significance ★ same type
CCAR2 p.Ala214Ser Uncertain significance ★ ⚠ same type
CCAR2 p.Ala293Gly 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/ccar2-p-thr461met (accessed [today's date]).

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