Is CAND1 p.Pro1187Ala (c.3559C>G) pathogenic?

CAND1 p.Pro1187Ala (c.3559C>G) is classified Uncertain significance in CAND1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely benign (0.1544); Very rare (popmax 0.000339%, nfe).

How common is CAND1 p.Pro1187Ala (c.3559C>G) in the general population?

CAND1 p.Pro1187Ala (c.3559C>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CAND1 p.Pro1187Ala (c.3559C>G)?

AlphaMissense predicts likely benign (score 0.1544) — an in-silico prediction, not a clinical call.

CAND1 p.Pro1187Ala

c.3559C>G · rs140637003 · VCV2301230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1544 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1544	likely benign
REVEL	0.5	indeterminate
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 135 bp · p 0.086 · regional, not allelic
Overall
CADD	25.6	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 0.000339% European (non-Finnish) · 4/1,179,696 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,380 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.Pro1187Ala
Coding: c.3559C>G
MANE Select: NM_018448
dbSNP: rs140637003
Type: single nucleotide variant
Location: chr12:67312696 (GRCh38)
Gene constraint: LOEUF 0.076 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.95 · 14 PDB
Residue 1187: a β-strand

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

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CAND1 p.Arg777His Uncertain significance ★ ⚠ same type
CAND1 p.Asn599Lys Uncertain significance ★ ⚠ same type
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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-pro1187ala (accessed [today's date]).

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