Is CMTM2 p.Pro241Leu (c.722C>T) pathogenic?

CMTM2 p.Pro241Leu (c.722C>T) is classified Uncertain significance in CMTM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely benign (0.1165); Absent from gnomAD v4.1.

How common is CMTM2 p.Pro241Leu (c.722C>T) in the general population?

CMTM2 p.Pro241Leu (c.722C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CMTM2 p.Pro241Leu (c.722C>T)?

AlphaMissense predicts likely benign (score 0.1165) — an in-silico prediction, not a clinical call.

CMTM2 p.Pro241Leu

c.722C>T · VCV3267993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1165 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1165	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -10.16	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 -2.8	GERP -2.3
Regional constraint	o/e 0.89	unconstrained · MANE · 8,508 bp · p 0.043 · regional, not allelic
Overall
CADD	3.492	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CMTM2
Protein: p.Pro241Leu
Coding: c.722C>T
MANE Select: NM_144673
Type: single nucleotide variant
Location: chr16:66588094 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.74
Residue 241: the 'disordered' region

Full CMTM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CMTM2 p.Ala181Ser Uncertain significance ★ ⚠ same type
CMTM2 p.Ala181Val Uncertain significance ★ ⚠ same type
CMTM2 p.Ala88Thr Uncertain significance ★ ⚠ same type
CMTM2 p.Ala9Thr Uncertain significance ★ ⚠ same type
CMTM2 p.Arg171Gln Uncertain significance ★ ⚠ same type
CMTM2 p.Arg171Trp Uncertain significance ★ ⚠ same type
CMTM2 p.Arg69Pro Uncertain significance ★ ⚠ same type
CMTM2 p.Arg70Cys 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/cmtm2-p-pro241leu (accessed [today's date]).

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