Is CAND2 p.Arg384Cys (c.1150C>T) pathogenic?

CAND2 p.Arg384Cys (c.1150C>T) is classified Uncertain significance in CAND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: ambiguous (0.3541); Very rare (popmax 0.00267%, afr).

How common is CAND2 p.Arg384Cys (c.1150C>T) in the general population?

CAND2 p.Arg384Cys (c.1150C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CAND2 p.Arg384Cys (c.1150C>T)?

AlphaMissense predicts ambiguous (score 0.3541) — an in-silico prediction, not a clinical call.

CAND2 p.Arg384Cys

c.1150C>T · VCV4648006

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3541 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
AlphaMissense	0.3541	ambiguous
REVEL	0.339	indeterminate
SaProt	LLR -8.10	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3	GERP -5, phastCons 0.99
Regional constraint	o/e 0.92	unconstrained · MANE · 27 kb · p 0.0026 · regional, not allelic
Overall
CADD	24.3	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 0.00267% African / African-American · 2/74,954 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000558% 9/1,613,860 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,477
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000508%	196,676

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.Arg384Cys
Coding: c.1150C>T
MANE Select: NM_001162499
Type: single nucleotide variant
Location: chr3:12815284 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.14 · 2 PDB
Residue 384: 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-arg384cys (accessed [today's date]).

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