Is CMTM7 p.Ser30Arg (c.90C>A) pathogenic?

CMTM7 p.Ser30Arg (c.90C>A) is classified Uncertain significance in CMTM7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.1556); Ultra-rare (popmax 0.0328%, nfe).

How common is CMTM7 p.Ser30Arg (c.90C>A) in the general population?

CMTM7 p.Ser30Arg (c.90C>A) is ultra-rare (popmax 0.0328%, nfe) (gnomAD).

What do computational predictors say about CMTM7 p.Ser30Arg (c.90C>A)?

AlphaMissense predicts likely benign (score 0.1556) — an in-silico prediction, not a clinical call.

CMTM7 p.Ser30Arg

c.90C>A · rs562211318 · VCV3146276

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1556 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0328%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1556	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.38	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 0.82	GERP 0.17, phastCons 0.091
Regional constraint	o/e 0.83	unconstrained · MANE · 62 kb · p 0.0095 · regional, not allelic
Overall
CADD	13.96	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 0.0328% European (non-Finnish) · 324/987,020 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0287%

Overall 0.0271% 335/1,233,962 alleles · ultra-rare exomes 322/1,081,726 · genomes 13/152,236 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0328%	3,046
Admixed American	0.0254%	3,940
Remaining individualsnot grpmax-eligible	0.00657%	15,231
African / African-American	0.0031%	32,220

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: CMTM7
Protein: p.Ser30Arg
Coding: c.90C>A
MANE Select: NM_138410
dbSNP: rs562211318
Type: single nucleotide variant
Location: chr3:32391996 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI 0.34 (gnomAD)
Structure: AlphaFold pLDDT 70.28

Full CMTM7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CMTM7 p.Ala144Val Uncertain significance ★ ⚠ same type
CMTM7 p.Ala150Ser Uncertain significance ★ ⚠ same type
CMTM7 p.Ala22Asp Uncertain significance ★ ⚠ same type
CMTM7 p.Ala22Val Uncertain significance ★ ⚠ same type
CMTM7 p.Ala73Thr Uncertain significance ★ ⚠ same type
CMTM7 p.Arg98Gly Uncertain significance ★ ⚠ same type
CMTM7 p.Arg98His Uncertain significance ★ ⚠ same type
CMTM7 p.Cys62Ser 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/cmtm7-p-ser30arg (accessed [today's date]).

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