Is CAND2 p.Arg825His (c.2474G>A) pathogenic?

CAND2 p.Arg825His (c.2474G>A) is classified Uncertain significance in CAND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely benign (0.0775); Very rare (popmax 0.00458%, nfe).

How common is CAND2 p.Arg825His (c.2474G>A) in the general population?

CAND2 p.Arg825His (c.2474G>A) is very rare (popmax 0.00458%, nfe) (gnomAD).

What do computational predictors say about CAND2 p.Arg825His (c.2474G>A)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

CAND2 p.Arg825His

c.2474G>A · rs747643034 · VCV3136959

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00458%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -10.89	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 2.9	GERP -2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 27 kb · p 0.0026 · regional, not allelic
Overall
CADD	21.6	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 0.00458% European (non-Finnish) · 54/1,180,020 alleles

Filtering AF 0.00358% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.00445% 65/1,461,340 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00787%	12,710
European (non-Finnish)grpmax	0.00458%	21,852
Remaining individualsnot grpmax-eligible	0.0032%	31,254
East Asian	0.00223%	44,886
South Asian	0.0022%	45,545
African / African-American	0.00133%	75,080

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg825His
Coding: c.2474G>A
MANE Select: NM_001162499
dbSNP: rs747643034
Type: single nucleotide variant
Location: chr3:12817406 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.14 · 2 PDB
Residue 825: 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-arg825his (accessed [today's date]).

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