Is CAND2 p.Arg953Gln (c.2858G>A) pathogenic?

CAND2 p.Arg953Gln (c.2858G>A) is classified Uncertain significance in CAND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.1854); Ultra-rare (popmax 0.0114%, eas).

How common is CAND2 p.Arg953Gln (c.2858G>A) in the general population?

CAND2 p.Arg953Gln (c.2858G>A) is ultra-rare (popmax 0.0114%, eas) (gnomAD).

What do computational predictors say about CAND2 p.Arg953Gln (c.2858G>A)?

AlphaMissense predicts likely benign (score 0.1854) — an in-silico prediction, not a clinical call.

CAND2 p.Arg953Gln

c.2858G>A · rs761170457 · VCV3136963

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1854 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0114%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1854	likely benign
REVEL	0.262	benign-leaning
SaProt	LLR -10.78	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 27 kb · p 0.0026 · regional, not allelic
Overall
CADD	29.9	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 0.0114% East Asian · 5/44,050 alleles

Filtering AF 0.00441% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0029%

Overall 0.0015% 23/1,529,404 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0114%	8,810
African / African-American	0.00554%	18,045
Admixed American	0.0043%	23,235
South Asian	0.0013%	76,696
European (non-Finnish)	0.000965%	103,628

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: CAND2
Protein: p.Arg953Gln
Coding: c.2858G>A
MANE Select: NM_001162499
dbSNP: rs761170457
Type: single nucleotide variant
Location: chr3:12817790 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.14 · 2 PDB
Residue 953: an α-helix

Full CAND2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAND2 p.Arg953Trp Uncertain significance ★ ⚠ same residue
CAND2 p.Arg768Cys Uncertain significance ★★ ⚠ same type
CAND2 p.Arg1028Cys Benign ★★ same type
CAND2 p.Arg987Gln Benign ★★ ⚠ same type
CAND2 p.His709Arg Benign ★★ same type
CAND2 p.Ser491= Benign ★★ same type
CAND2 p.Ser999= Likely benign ★★ same type
CAND2 p.Ala1187Val 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/cand2-p-arg953gln (accessed [today's date]).

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