Is CAND2 p.Ser480Leu (c.1439C>T) pathogenic?

CAND2 p.Ser480Leu (c.1439C>T) is classified Uncertain significance in CAND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.1276); Very rare (popmax 0.00134%, afr).

How common is CAND2 p.Ser480Leu (c.1439C>T) in the general population?

CAND2 p.Ser480Leu (c.1439C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CAND2 p.Ser480Leu (c.1439C>T)?

AlphaMissense predicts likely benign (score 0.1276) — an in-silico prediction, not a clinical call.

CAND2 p.Ser480Leu

c.1439C>T · rs1290513545 · VCV2476320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1276 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1276	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -10.22	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.30	donor gain · deltas
Pangolin	Δ0.23	loss · gain 0.11 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, 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 0.00134% African / African-American · 1/74,880 alleles

Overall 0.000657% 1/152,164 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.Ser480Leu
Coding: c.1439C>T
MANE Select: NM_001162499
dbSNP: rs1290513545
Type: single nucleotide variant
Location: chr3:12816006 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.14 · 2 PDB
Residue 480: 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-ser480leu (accessed [today's date]).

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