Is CAND1 p.Val503Ile (c.1507G>A) pathogenic?

CAND1 p.Val503Ile (c.1507G>A) is classified Uncertain significance in CAND1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). AlphaMissense: likely benign (0.1068); Ultra-rare (popmax 0.0483%, sas).

How common is CAND1 p.Val503Ile (c.1507G>A) in the general population?

CAND1 p.Val503Ile (c.1507G>A) is ultra-rare (popmax 0.0483%, sas) (gnomAD).

What do computational predictors say about CAND1 p.Val503Ile (c.1507G>A)?

AlphaMissense predicts likely benign (score 0.1068) — an in-silico prediction, not a clinical call.

CAND1 p.Val503Ile

c.1507G>A · VCV3484634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1068 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0483%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1068	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -7.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 14 kb · p 1.4e-15 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0483% South Asian · 44/91,080 alleles

Filtering AF 0.0369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00428% 69/1,613,914 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0483%	2,070
African / African-American	0.016%	6,250
Remaining individualsnot grpmax-eligible	0.0144%	6,944
Admixed American	0.00167%	60,014
European (non-Finnish)	0.000254%	393,287

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.Val503Ile
Coding: c.1507G>A
MANE Select: NM_018448
Type: single nucleotide variant
Location: chr12:67305175 (GRCh38)
Gene constraint: LOEUF 0.076 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.95 · 14 PDB
Residue 503: an α-helix

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

Similar variants

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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-val503ile (accessed [today's date]).

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