Is CMC1 p.Met23Val (c.67A>G) pathogenic?

CMC1 p.Met23Val (c.67A>G) is classified Uncertain significance in CMC1 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-08-19). AlphaMissense: likely benign (0.1394); Very rare (popmax 8.49e-05%, nfe).

How common is CMC1 p.Met23Val (c.67A>G) in the general population?

CMC1 p.Met23Val (c.67A>G) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about CMC1 p.Met23Val (c.67A>G)?

AlphaMissense predicts likely benign (score 0.1394) — an in-silico prediction, not a clinical call.

CMC1 p.Met23Val

c.67A>G · rs771878791 · VCV2246529

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1394 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1394	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -13.44	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 78 kb · p 0.77 · regional, not allelic
Overall
CADD	21.7	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 8.49e-05% European (non-Finnish) · 1/1,178,166 alleles

Overall 6.86e-05% 1/1,457,608 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: CMC1
Protein: p.Met23Val
Coding: c.67A>G
MANE Select: NM_182523
dbSNP: rs771878791
Type: single nucleotide variant
Location: chr3:28263338 (GRCh38)
Gene constraint: LOEUF 1.906 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 87.18

Full CMC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CMC1 p.Ala2Ser Uncertain significance ★ ⚠ same type
CMC1 p.Ala2Val Uncertain significance ★ ⚠ same type
CMC1 p.Arg11Thr Uncertain significance ★ ⚠ same type
CMC1 p.Arg85Met Uncertain significance ★ ⚠ same type
CMC1 p.Asp37Gly Uncertain significance ★ ⚠ same type
CMC1 p.Asp4Asn Uncertain significance ★ ⚠ same type
CMC1 p.Cys42Tyr Uncertain significance ★ ⚠ same type
CMC1 p.Cys77Gly 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/cmc1-p-met23val (accessed [today's date]).

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