Is TRPM5 p.Pro7Ser (c.19C>T) pathogenic?

TRPM5 p.Pro7Ser (c.19C>T) is classified Likely benign in TRPM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-04). AlphaMissense: likely benign (0.066); Ultra-rare (popmax 0.0165%, mid).

How common is TRPM5 p.Pro7Ser (c.19C>T) in the general population?

TRPM5 p.Pro7Ser (c.19C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about TRPM5 p.Pro7Ser (c.19C>T)?

AlphaMissense predicts likely benign (score 0.066) — an in-silico prediction, not a clinical call.

TRPM5 p.Pro7Ser

c.19C>T · VCV3811075

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.066 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.066	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.09	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 -2	GERP -2.1
Overall
CADD	0.007	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

Grpmax group 0.0165% Middle Eastern · 1/6,048 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,611,944 alleles · ultra-rare exomes 2/1,459,790 · genomes 1/152,154 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,048
African / African-American	0.00267%	37,451

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: TRPM5
Protein: p.Pro7Ser
Coding: c.19C>T
MANE Select: NM_014555
Type: single nucleotide variant
Location: chr11:2423018 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.66

Full TRPM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRPM5 p.Ala574= Benign ★★ same type
TRPM5 p.Arg500Gln Likely benign ★★ same type
TRPM5 p.Cys227= Benign ★★ same type
TRPM5 p.Gly1136Ser Benign ★★ same type
TRPM5 p.Pro455= Benign/Likely benign ★★ same type
TRPM5 p.Thr218= Benign ★★ same type
TRPM5 p.Thr314= Benign/Likely benign ★★ same type
TRPM5 p.Thr616= Benign ★★ 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/trpm5-p-pro7ser (accessed [today's date]).

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