Is CNOT11 p.Met212Val (c.634A>G) pathogenic?

CNOT11 p.Met212Val (c.634A>G) is classified Uncertain significance in CNOT11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-19). AlphaMissense: likely benign (0.0775); Ultra-rare (popmax 0.0714%, sas).

How common is CNOT11 p.Met212Val (c.634A>G) in the general population?

CNOT11 p.Met212Val (c.634A>G) is ultra-rare (popmax 0.0714%, sas) (gnomAD).

What do computational predictors say about CNOT11 p.Met212Val (c.634A>G)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

CNOT11 p.Met212Val

c.634A>G · rs548449654 · VCV2593492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0714%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -6.52	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 5.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 127 bp · p 0.0001 · regional, not allelic
Overall
CADD	18.85	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 0.0714% South Asian · 65/91,062 alleles

Filtering AF 0.0574% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.00477% 77/1,614,146 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0714%	1,401
Remaining individualsnot grpmax-eligible	0.0048%	20,836
European (non-Finnish)	0.000763%	131,110

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: CNOT11
Protein: p.Met212Val
Coding: c.634A>G
MANE Select: NM_017546
dbSNP: rs548449654
Type: single nucleotide variant
Location: chr2:101257910 (GRCh38)
Gene constraint: LOEUF 0.583 · pLI 0.77 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 4 PDB
Residue 212: an α-helix

Full CNOT11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNOT11 p.Ala365Pro Uncertain significance ★ ⚠ same type
CNOT11 p.Arg202Cys Uncertain significance ★ ⚠ same type
CNOT11 p.Arg202His Uncertain significance ★ ⚠ same type
CNOT11 p.Arg286Cys Uncertain significance ★ ⚠ same type
CNOT11 p.Arg60Ser Uncertain significance ★ ⚠ same type
CNOT11 p.Asp307Glu Uncertain significance ★ ⚠ same type
CNOT11 p.Gln203His Uncertain significance ★ ⚠ same type
CNOT11 p.Gly36Ser 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/cnot11-p-met212val (accessed [today's date]).

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