Is CAND2 p.Ala1136Val (c.3407C>T) pathogenic?

CAND2 p.Ala1136Val (c.3407C>T) is classified Benign in CAND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-14). AlphaMissense: likely benign (0.1947); Common (popmax 5.97%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CAND2 p.Ala1136Val (c.3407C>T)?

AlphaMissense predicts likely benign (score 0.1947) — an in-silico prediction, not a clinical call.

CAND2 p.Ala1136Val

Q: How common is CAND2 p.Ala1136Val (c.3407C>T) in the general population?

CAND2 p.Ala1136Val (c.3407C>T) is common (popmax 5.97%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3407C>T · rs75387493 · VCV787971

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1947 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.97%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1947	likely benign
REVEL	0.258	benign-leaning
SaProt	LLR -7.75	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 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 27 kb · p 0.0026 · regional, not allelic
Overall
CADD	22.4	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 5.97% East Asian · 2,680/44,874 alleles

Filtering AF 5.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.71%

Overall 0.192% 3,101/1,614,084 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	5.97%	17
Remaining individualsnot grpmax-eligible	0.341%	293
South Asian	0.139%	717
Middle Eastern	0.0495%	2,021
African / African-American	0.0347%	2,886
Admixed American	0.0317%	3,159
European (non-Finnish)	0.0028%	35,757

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.Ala1136Val
Coding: c.3407C>T
MANE Select: NM_001162499
dbSNP: rs75387493
Type: single nucleotide variant
Location: chr3:12831496 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.14 · 2 PDB
Residue 1136: 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-ala1136val (accessed [today's date]).

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