Is CAND2 p.Val402Met (c.1204G>A) pathogenic?

CAND2 p.Val402Met (c.1204G>A) is classified Uncertain significance in CAND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-02). AlphaMissense: likely benign (0.096); Very rare (popmax 0.00445%, eas).

How common is CAND2 p.Val402Met (c.1204G>A) in the general population?

CAND2 p.Val402Met (c.1204G>A) is very rare (popmax 0.00445%, eas) (gnomAD).

What do computational predictors say about CAND2 p.Val402Met (c.1204G>A)?

AlphaMissense predicts likely benign (score 0.096) — an in-silico prediction, not a clinical call.

CAND2 p.Val402Met

c.1204G>A · rs752676710 · VCV2407013

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.096 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.096	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -7.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.36	GERP -5
Regional constraint	o/e 0.92	unconstrained · MANE · 27 kb · p 0.0026 · regional, not allelic
Overall
CADD	15.85	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 0.00445% East Asian · 2/44,898 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00198% 32/1,613,868 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,449
African / African-American	0.004%	24,979
Remaining individualsnot grpmax-eligible	0.0032%	31,239
European (non-Finnish)	0.00203%	49,169
Admixed American	0.00167%	60,004

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.Val402Met
Coding: c.1204G>A
MANE Select: NM_001162499
dbSNP: rs752676710
Type: single nucleotide variant
Location: chr3:12815338 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.14 · 2 PDB
Residue 402: an α-helix

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

Similar variants

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
CAND2 p.Ala1215Thr 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-val402met (accessed [today's date]).

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