Is CMTM2 p.Pro17Gln (c.50C>A) pathogenic?

CMTM2 p.Pro17Gln (c.50C>A) is classified Uncertain significance in CMTM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). AlphaMissense: likely benign (0.1181); Ultra-rare (popmax 0.0507%, afr).

How common is CMTM2 p.Pro17Gln (c.50C>A) in the general population?

CMTM2 p.Pro17Gln (c.50C>A) is ultra-rare (popmax 0.0507%, afr) (gnomAD).

What do computational predictors say about CMTM2 p.Pro17Gln (c.50C>A)?

AlphaMissense predicts likely benign (score 0.1181) — an in-silico prediction, not a clinical call.

CMTM2 p.Pro17Gln

c.50C>A · rs145030670 · VCV2337187

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1181 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0507%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1181	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -8.55	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 -0.77	GERP -1.1
Regional constraint	o/e 0.89	unconstrained · MANE · 8,508 bp · p 0.043 · regional, not allelic
Overall
CADD	12.28	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 0.0507% African / African-American · 38/74,880 alleles

Filtering AF 0.038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0335%

Overall 0.00279% 45/1,613,842 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0507%	1,971
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.008%	12,497
Admixed American	0.00167%	60,010

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: CMTM2
Protein: p.Pro17Gln
Coding: c.50C>A
MANE Select: NM_144673
dbSNP: rs145030670
Type: single nucleotide variant
Location: chr16:66579657 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.74
Residue 17: 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-pro17gln (accessed [today's date]).

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