Is CAND2 p.Leu796Gln (c.2387T>A) pathogenic?

CAND2 p.Leu796Gln (c.2387T>A) is classified Uncertain significance in CAND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely benign (0.1618); Very rare (popmax 0.004%, afr).

How common is CAND2 p.Leu796Gln (c.2387T>A) in the general population?

CAND2 p.Leu796Gln (c.2387T>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CAND2 p.Leu796Gln (c.2387T>A)?

AlphaMissense predicts likely benign (score 0.1618) — an in-silico prediction, not a clinical call.

CAND2 p.Leu796Gln

c.2387T>A · VCV4648024

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1618 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1618	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -10.40	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 4.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 27 kb · p 0.0026 · regional, not allelic
Overall
CADD	19.58	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 0.004% African / African-American · 3/74,952 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00197% 3/152,232 alleles · very rare

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.Leu796Gln
Coding: c.2387T>A
MANE Select: NM_001162499
Type: single nucleotide variant
Location: chr3:12817319 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.14 · 2 PDB
Residue 796: an α-helix

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

Similar variants

CAND2 p.Leu796Arg 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-leu796gln (accessed [today's date]).

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