Is CAND2 p.Arg1028Cys (c.3082C>T) pathogenic?

CAND2 p.Arg1028Cys (c.3082C>T) is classified Benign in CAND2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-03-01). AlphaMissense: likely pathogenic (0.5652); Low-frequency (popmax 3.05%, amr).

How common is CAND2 p.Arg1028Cys (c.3082C>T) in the general population?

CAND2 p.Arg1028Cys (c.3082C>T) is low-frequency (popmax 3.05%, amr) (gnomAD).

What do computational predictors say about CAND2 p.Arg1028Cys (c.3082C>T)?

AlphaMissense predicts likely pathogenic (score 0.5652) — an in-silico prediction, not a clinical call.

CAND2 p.Arg1028Cys

c.3082C>T · rs139572691 · VCV783215

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5652 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.05%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5652	likely pathogenic
REVEL	0.524	indeterminate
SaProt	LLR -11.20	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.07, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 27 kb · p 0.0026 · regional, not allelic
Overall
CADD	32.0	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 3.05% Admixed American · 1,663/54,454 alleles

Filtering AF 2.93% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.88%

Overall 0.172% 2,723/1,580,888 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	3.05%	33
East Asian	0.354%	282
South Asian	0.197%	508
Remaining individualsnot grpmax-eligible	0.175%	573
Ashkenazi Jewishnot grpmax-eligible	0.163%	614
Middle Eastern	0.15%	669
African / African-American	0.0536%	1,866
European (non-Finnish)	0.0455%	2,198
Finnishnot grpmax-eligible	0.00486%	20,556

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.Arg1028Cys
Coding: c.3082C>T
MANE Select: NM_001162499
dbSNP: rs139572691
Type: single nucleotide variant
Location: chr3:12825511 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.14 · 2 PDB
Residue 1028: an α-helix

Full CAND2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAND2 p.Arg1028Leu Uncertain significance ★ ⚠ same residue
CAND2 p.Arg768Cys Uncertain significance ★★ ⚠ 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-arg1028cys (accessed [today's date]).

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