Is CAMTA2 p.Cys63Arg (c.187T>C) pathogenic?

CAMTA2 p.Cys63Arg (c.187T>C) is classified Uncertain significance in CAMTA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: likely pathogenic (0.6955); Ultra-rare (popmax 0.0381%, nfe).

How common is CAMTA2 p.Cys63Arg (c.187T>C) in the general population?

CAMTA2 p.Cys63Arg (c.187T>C) is ultra-rare (popmax 0.0381%, nfe) (gnomAD).

What do computational predictors say about CAMTA2 p.Cys63Arg (c.187T>C)?

AlphaMissense predicts likely pathogenic (score 0.6955) — an in-silico prediction, not a clinical call.

CAMTA2 p.Cys63Arg

c.187T>C · rs201830300 · VCV2592131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6955 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0381%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6955	likely pathogenic
REVEL	0.178	moderately benign-leaning
SaProt	LLR -6.16	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 11	GERP 0.48, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 4,433 bp · p 5.1e-10 · regional, not allelic
Overall
CADD	24.7	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 0.0381% European (non-Finnish) · 449/1,180,024 alleles

Filtering AF 0.0351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0339%

Overall 0.0308% 497/1,614,052 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0464%	2,155
European (non-Finnish)grpmax	0.0381%	2,628
Admixed American	0.0117%	8,571
African / African-American	0.00667%	14,985
South Asian	0.00549%	18,218
Finnishnot grpmax-eligible	0.00312%	32,020

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CAMTA2
Protein: p.Cys63Arg
Coding: c.187T>C
MANE Select: NM_015099
dbSNP: rs201830300
Type: single nucleotide variant
Location: chr17:4982992 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 60.82
Residue 63: a DNA-binding region

Full CAMTA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAMTA2 p.Ala267Pro Benign ★★ same type
CAMTA2 p.His343= Benign ★★ same type
CAMTA2 p.Pro749= Benign ★★ same type
CAMTA2 c.1765+1G>A Uncertain significance ★ same type
CAMTA2 c.1901-2A>C Uncertain significance ★ same type
CAMTA2 c.-18C>G Uncertain significance ★ same type
CAMTA2 c.-2C>A Uncertain significance ★ same type
CAMTA2 c.-32C>T 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/camta2-p-cys63arg (accessed [today's date]).

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