Is CAND1 p.Asp675Val (c.2024A>T) pathogenic?

CAND1 p.Asp675Val (c.2024A>T) is classified Uncertain significance in CAND1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely pathogenic (0.8441); Very rare (popmax 0.000169%, nfe).

How common is CAND1 p.Asp675Val (c.2024A>T) in the general population?

CAND1 p.Asp675Val (c.2024A>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CAND1 p.Asp675Val (c.2024A>T)?

AlphaMissense predicts likely pathogenic (score 0.8441) — an in-silico prediction, not a clinical call.

CAND1 p.Asp675Val

c.2024A>T · VCV4647998

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8441 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8441	likely pathogenic
REVEL	0.462	indeterminate
SaProt	LLR -11.05	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 9.4	GERP 0.49, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 14 kb · p 1.4e-15 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,978 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,726 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: CAND1
Protein: p.Asp675Val
Coding: c.2024A>T
MANE Select: NM_018448
Type: single nucleotide variant
Location: chr12:67305692 (GRCh38)
Gene constraint: LOEUF 0.076 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.95 · 14 PDB
Residue 675: an α-helix

Full CAND1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAND1 p.Ala1209Glu Uncertain significance ★ ⚠ same type
CAND1 p.Ala1209Val Uncertain significance ★ ⚠ same type
CAND1 p.Ala378Thr Uncertain significance ★ ⚠ same type
CAND1 p.Ala561Val Uncertain significance ★ ⚠ same type
CAND1 p.Arg777His Uncertain significance ★ ⚠ same type
CAND1 p.Asn599Lys Uncertain significance ★ ⚠ same type
CAND1 p.Asn599Ser Uncertain significance ★ ⚠ same type
CAND1 p.Asn736Ser 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/cand1-p-asp675val (accessed [today's date]).

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