Is TMEM151A p.Leu22Pro (c.65T>C) pathogenic?

TMEM151A p.Leu22Pro (c.65T>C) is classified Uncertain significance in TMEM151A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: likely benign (0.0652); No allele count reported in gnomAD v4.1 (AN 1,480,644); Associated with Inborn genetic diseases.

What condition is associated with TMEM151A p.Leu22Pro (c.65T>C)?

TMEM151A p.Leu22Pro (c.65T>C) is associated with Inborn genetic diseases (ClinVar).

How common is TMEM151A p.Leu22Pro (c.65T>C) in the general population?

TMEM151A p.Leu22Pro (c.65T>C) is no allele count reported in gnomAD v4.1 (AN 1,480,644) (gnomAD).

What do computational predictors say about TMEM151A p.Leu22Pro (c.65T>C)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

TMEM151A p.Leu22Pro

c.65T>C · VCV4186265

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,480,644)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.227	benign-leaning
SaProt	LLR -5.08	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 3.1	GERP 0.85, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 2,899 bp · p 0.21 · regional, not allelic
Overall
CADD	21.0	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

No allele count reported in gnomAD v4.1 (AN 1,480,644). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TMEM151A
Protein: p.Leu22Pro
Coding: c.65T>C
MANE Select: NM_153266
Type: single nucleotide variant
Location: chr11:66292078 (GRCh38)
Gene constraint: LOEUF 1.322 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.63
Residue 22: 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.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
TMEM151A p.Ala467Val 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-leu22pro (accessed [today's date]).

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