Is CIMAP2 p.Val31Met (c.91G>A) pathogenic?

CIMAP2 p.Val31Met (c.91G>A) is classified Uncertain significance in CIMAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-23). AlphaMissense: likely benign (0.3384); Ultra-rare (popmax 0.0141%, nfe).

How common is CIMAP2 p.Val31Met (c.91G>A) in the general population?

CIMAP2 p.Val31Met (c.91G>A) is ultra-rare (popmax 0.0141%, nfe) (gnomAD).

What do computational predictors say about CIMAP2 p.Val31Met (c.91G>A)?

AlphaMissense predicts likely benign (score 0.3384) — an in-silico prediction, not a clinical call.

CIMAP2 p.Val31Met

c.91G>A · rs569094306 · VCV2302924

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3384 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0141%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3384	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -7.52	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 3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 36 kb · p 0.61 · regional, not allelic
Overall
CADD	25.0	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 0.0141% European (non-Finnish) · 162/1,147,020 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0117%

Overall 0.011% 170/1,540,246 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0141%	7,080
Remaining individualsnot grpmax-eligible	0.00839%	11,918
African / African-American	0.00422%	23,713

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: CIMAP2
Protein: p.Val31Met
Coding: c.91G>A
MANE Select: NM_001110533
dbSNP: rs569094306
Type: single nucleotide variant
Location: chr1:54806207 (GRCh38)
Structure: AlphaFold pLDDT 64.45

Full CIMAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMAP2 p.Val31Leu Uncertain significance ★ ⚠ same residue
CIMAP2 p.Ala7Val Uncertain significance ★ ⚠ same type
CIMAP2 p.Ala8Thr Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg117Trp Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg145Trp Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg186Gln Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg203Trp Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg232Cys 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/cimap2-p-val31met (accessed [today's date]).

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