Is CAND2 p.Ala884Val (c.2651C>T) pathogenic?

CAND2 p.Ala884Val (c.2651C>T) is classified Uncertain significance in CAND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-20). AlphaMissense: ambiguous (0.484); Very rare (popmax 0.00602%, nfe).

How common is CAND2 p.Ala884Val (c.2651C>T) in the general population?

CAND2 p.Ala884Val (c.2651C>T) is very rare (popmax 0.00602%, nfe) (gnomAD).

What do computational predictors say about CAND2 p.Ala884Val (c.2651C>T)?

AlphaMissense predicts ambiguous (score 0.484) — an in-silico prediction, not a clinical call.

CAND2 p.Ala884Val

c.2651C>T · rs373807883 · VCV2602709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.484 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00602%, nfe)

Computational evidence

Protein change
AlphaMissense	0.484	ambiguous
REVEL	0.389	indeterminate
SaProt	LLR -9.61	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 27 kb · p 0.0026 · regional, not allelic
Overall
CADD	26.2	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 0.00602% European (non-Finnish) · 71/1,180,024 alleles

Filtering AF 0.00486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00471% 76/1,613,808 alleles · very rare exomes 70/1,461,542 · genomes 6/152,266 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00602%	16,620
Remaining individualsnot grpmax-eligible	0.0048%	20,826
East Asian	0.00223%	44,894
African / African-American	0.00133%	74,960

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.Ala884Val
Coding: c.2651C>T
MANE Select: NM_001162499
dbSNP: rs373807883
Type: single nucleotide variant
Location: chr3:12817583 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.14 · 2 PDB
Residue 884: 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-ala884val (accessed [today's date]).

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