Is TMEM151A p.Pro325Ser (c.973C>T) pathogenic?

TMEM151A p.Pro325Ser (c.973C>T) is classified Uncertain significance in TMEM151A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.0631); Ultra-rare (popmax 0.0131%, amr); Associated with Inborn genetic diseases.

What condition is associated with TMEM151A p.Pro325Ser (c.973C>T)?

TMEM151A p.Pro325Ser (c.973C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TMEM151A p.Pro325Ser (c.973C>T) in the general population?

TMEM151A p.Pro325Ser (c.973C>T) is ultra-rare (popmax 0.0131%, amr) (gnomAD).

What do computational predictors say about TMEM151A p.Pro325Ser (c.973C>T)?

AlphaMissense predicts likely benign (score 0.0631) — an in-silico prediction, not a clinical call.

TMEM151A p.Pro325Ser

c.973C>T · rs1207311765 · VCV2466194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0631 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0131%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0631	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -6.32	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 2.7	GERP -3.7, phastCons 0.98
Regional constraint	o/e 1.12	unconstrained · MANE · 699 bp · p 0.026 · regional, not allelic
Overall
CADD	11.18	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 0.0131% Admixed American · 7/53,390 alleles

Filtering AF 0.00613% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00429%

Overall 0.000638% 10/1,566,172 alleles · ultra-rare exomes 8/1,414,076 · genomes 2/152,096 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0131%	7,627
Remaining individualsnot grpmax-eligible	0.0033%	30,295
European (non-Finnish)	8.64e-05%	1,156,779

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: TMEM151A
Protein: p.Pro325Ser
Coding: c.973C>T
MANE Select: NM_153266
dbSNP: rs1207311765
Type: single nucleotide variant
Location: chr11:66295219 (GRCh38)
Gene constraint: LOEUF 1.322 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.63
Residue 325: a UniProt-annotated variant site (in ekd3)

Full TMEM151A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TMEM151A p.Pro325Ala Uncertain significance ★ ⚠ same residue
TMEM151A p.Ala137Glu Uncertain significance ★ ⚠ same condition
TMEM151A p.Ala197Pro Uncertain significance ★ ⚠ same condition
TMEM151A p.Ala197Val Uncertain significance ★ ⚠ same condition
TMEM151A p.Ala211Val Uncertain significance ★ ⚠ same condition
TMEM151A p.Ala274Thr Uncertain significance ★ ⚠ same condition
TMEM151A p.Ala304Asp Uncertain significance ★ ⚠ same condition
TMEM151A p.Ala392Gly Uncertain significance ★ ⚠ same condition

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/tmem151a-p-pro325ser (accessed [today's date]).

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