Is CAND2 p.Arg987Gln (c.2960G>A) pathogenic?

CAND2 p.Arg987Gln (c.2960G>A) is classified Benign in CAND2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-11). AlphaMissense: ambiguous (0.3625); Low-frequency (popmax 3.3%, amr).

How common is CAND2 p.Arg987Gln (c.2960G>A) in the general population?

CAND2 p.Arg987Gln (c.2960G>A) is low-frequency (popmax 3.3%, amr) (gnomAD).

What do computational predictors say about CAND2 p.Arg987Gln (c.2960G>A)?

AlphaMissense predicts ambiguous (score 0.3625) — an in-silico prediction, not a clinical call.

CAND2 p.Arg987Gln

c.2960G>A · rs181307051 · VCV769601

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3625 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.3%, amr)

Computational evidence

Protein change
AlphaMissense	0.3625	ambiguous
REVEL	0.475	indeterminate
SaProt	LLR -11.14	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 27 kb · p 0.0026 · regional, not allelic
Overall
CADD	33.0	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 3.3% Admixed American · 1,978/60,002 alleles

Filtering AF 3.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.13%

Overall 0.166% 2,682/1,614,084 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	3.3%	30
East Asian	0.517%	193
Remaining individualsnot grpmax-eligible	0.218%	460
African / African-American	0.0586%	1,705
South Asian	0.0439%	2,277
European (non-Finnish)	0.021%	4,758
Middle Eastern	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,868

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.Arg987Gln
Coding: c.2960G>A
MANE Select: NM_001162499
dbSNP: rs181307051
Type: single nucleotide variant
Location: chr3:12820101 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.14 · 2 PDB
Residue 987: 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.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
CAND2 p.Ala171Thr 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-arg987gln (accessed [today's date]).

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