Is CMTM5 p.Ala43= (c.129C>T) pathogenic?

CMTM5 p.Ala43= (c.129C>T) is classified Benign in CMTM5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-21). Common (popmax 6.47%, afr) — too common for a highly-penetrant pathogenic allele.

CMTM5 p.Ala43=

Q: How common is CMTM5 p.Ala43= (c.129C>T) in the general population?

CMTM5 p.Ala43= (c.129C>T) is common (popmax 6.47%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.129C>T · rs56771760 · VCV788890

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.47%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.089	GERP -0.16, phastCons 0.9
Overall
CADD	13.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.47% African / African-American · 4,852/74,958 alleles

Filtering AF 6.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.26%

Overall 0.342% 5,512/1,613,900 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.47%	15
Admixed American	0.463%	216
Remaining individualsnot grpmax-eligible	0.44%	227
Middle Eastern	0.215%	466
South Asian	0.0121%	8,279
European (non-Finnish)	0.00703%	14,216

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: CMTM5
Protein: p.Ala43=
Coding: c.129C>T
MANE Select: NM_001288746
dbSNP: rs56771760
Type: single nucleotide variant
Location: chr14:23378351 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.83
Residue 43: the marvel domain

Full CMTM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CMTM5 p.Ala43Ser Uncertain significance ★ ⚠ same residue
CMTM5 p.Leu74= Benign ★★ same type
CMTM5 p.Ala217Thr Uncertain significance ★ ⚠ same type
CMTM5 p.Ala24Thr Uncertain significance ★ ⚠ same type
CMTM5 p.Ala62Thr Uncertain significance ★ ⚠ same type
CMTM5 p.Ala62Val Uncertain significance ★ ⚠ same type
CMTM5 p.Ala63Val Uncertain significance ★ ⚠ same type
CMTM5 p.Arg10Gln 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/cmtm5-p-ala43 (accessed [today's date]).

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