Is CMTR2 p.Met279Val (c.835A>G) pathogenic?

CMTR2 p.Met279Val (c.835A>G) is classified Uncertain significance in CMTR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-30). AlphaMissense: likely benign (0.1151); Ultra-rare (popmax 0.0165%, mid).

How common is CMTR2 p.Met279Val (c.835A>G) in the general population?

CMTR2 p.Met279Val (c.835A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CMTR2 p.Met279Val (c.835A>G)?

AlphaMissense predicts likely benign (score 0.1151) — an in-silico prediction, not a clinical call.

CMTR2 p.Met279Val

c.835A>G · rs1268193064 · VCV3146303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1151 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1151	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -5.13	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 2.6	GERP -2.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 2,309 bp · p 0.74 · regional, not allelic
Overall
CADD	16.25	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00161% 26/1,613,984 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0048%	20,835
Admixed American	0.00333%	30,009
European (non-Finnish)	0.00161%	62,098
African / African-American	0.00133%	75,044

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: CMTR2
Protein: p.Met279Val
Coding: c.835A>G
MANE Select: NM_018348
dbSNP: rs1268193064
Type: single nucleotide variant
Location: chr16:71285086 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.01
Residue 279: the adrift-type sam-dependent 2'-o-mtase domain

Full CMTR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CMTR2 p.Ala16Pro Uncertain significance ★ ⚠ same type
CMTR2 p.Ala16Thr Uncertain significance ★ ⚠ same type
CMTR2 p.Ala16Val Uncertain significance ★ ⚠ same type
CMTR2 p.Ala262Ser Uncertain significance ★ ⚠ same type
CMTR2 p.Ala31Ser Uncertain significance ★ ⚠ same type
CMTR2 p.Ala388Val Uncertain significance ★ ⚠ same type
CMTR2 p.Ala530Gly Uncertain significance ★ ⚠ same type
CMTR2 p.Ala684Thr 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/cmtr2-p-met279val (accessed [today's date]).

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