Is CAND2 p.Arg806Trp (c.2416C>T) pathogenic?

CAND2 p.Arg806Trp (c.2416C>T) is classified Uncertain significance in CAND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely benign (0.2417); Ultra-rare (popmax 0.0371%, nfe).

How common is CAND2 p.Arg806Trp (c.2416C>T) in the general population?

CAND2 p.Arg806Trp (c.2416C>T) is ultra-rare (popmax 0.0371%, nfe) (gnomAD).

What do computational predictors say about CAND2 p.Arg806Trp (c.2416C>T)?

AlphaMissense predicts likely benign (score 0.2417) — an in-silico prediction, not a clinical call.

CAND2 p.Arg806Trp

c.2416C>T · rs201715663 · VCV3136957

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2417 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0371%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2417	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -12.23	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -2.4, phastCons 0.93
Regional constraint	o/e 0.92	unconstrained · MANE · 27 kb · p 0.0026 · regional, not allelic
Overall
CADD	26.4	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 0.0371% European (non-Finnish) · 438/1,180,034 alleles

Filtering AF 0.0342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0331%

Overall 0.0289% 466/1,613,898 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0371%	2,694
Remaining individualsnot grpmax-eligible	0.0288%	3,473
Middle Eastern	0.0165%	6,052
Admixed American	0.01%	10,004
African / African-American	0.004%	25,024

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.Arg806Trp
Coding: c.2416C>T
MANE Select: NM_001162499
dbSNP: rs201715663
Type: single nucleotide variant
Location: chr3:12817348 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.14 · 2 PDB
Residue 806: an α-helix

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

Similar variants

CAND2 p.Arg806Gln Uncertain significance ★ ⚠ same residue
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

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-arg806trp (accessed [today's date]).

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