Is TMPRSS4 p.Pro182Ala (c.544C>G) pathogenic?

TMPRSS4 p.Pro182Ala (c.544C>G) is classified Uncertain significance in TMPRSS4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-26). AlphaMissense: likely benign (0.0691); Absent from gnomAD v4.1.

How common is TMPRSS4 p.Pro182Ala (c.544C>G) in the general population?

TMPRSS4 p.Pro182Ala (c.544C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TMPRSS4 p.Pro182Ala (c.544C>G)?

AlphaMissense predicts likely benign (score 0.0691) — an in-silico prediction, not a clinical call.

TMPRSS4 p.Pro182Ala

c.544C>G · rs748690185 · VCV2606384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0691 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0691	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -5.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.28	GERP -3
Regional constraint	o/e 0.98	unconstrained · MANE · 41 kb · p 0.65 · regional, not allelic
Overall
CADD	7.338	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

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: TMPRSS4
Protein: p.Pro182Ala
Coding: c.544C>G
MANE Select: NM_019894
dbSNP: rs748690185
Type: single nucleotide variant
Location: chr11:118108857 (GRCh38)
Gene constraint: LOEUF 0.94 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.01
Residue 182: a disulfide bond; the srcr domain

Full TMPRSS4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TMPRSS4 p.Pro182Ser Uncertain significance ★ ⚠ same residue
CAP2 p.Arg17His Uncertain significance ★★ ⚠ same type
CAP2 p.His203Arg Uncertain significance ★★ ⚠ same type
TMPRSS4 p.Ala44Val Likely benign ★★ same type
CAP2 c.1003-5T>G Uncertain significance ★ same type
CAP2 p.Ala162Thr Uncertain significance ★ ⚠ same type
CAP2 p.Ala262Pro Uncertain significance ★ ⚠ same type
CAP2 p.Ala272Thr 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/tmprss4-p-pro182ala (accessed [today's date]).

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