Is TEX11 p.Ile125Met (c.375C>G) pathogenic?

TEX11 p.Ile125Met (c.375C>G) is classified Uncertain significance in TEX11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely benign (0.0803); Very rare (popmax 0.00705%, sas); Associated with Inborn genetic diseases.

What condition is associated with TEX11 p.Ile125Met (c.375C>G)?

TEX11 p.Ile125Met (c.375C>G) is associated with Inborn genetic diseases (ClinVar).

How common is TEX11 p.Ile125Met (c.375C>G) in the general population?

TEX11 p.Ile125Met (c.375C>G) is very rare (popmax 0.00705%, sas) (gnomAD).

What do computational predictors say about TEX11 p.Ile125Met (c.375C>G)?

AlphaMissense predicts likely benign (score 0.0803) — an in-silico prediction, not a clinical call.

TEX11 p.Ile125Met

c.375C>G · VCV4632997

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0803 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00705%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0803	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -4.74	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 -5	GERP -3.1
Regional constraint	o/e 0.83	unconstrained · MANE · 379 kb · p 2e-05 · regional, not allelic
Overall
CADD	0.003	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I140M vs ClinVar I125M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00705% South Asian · 4/56,741 alleles

Filtering AF 0.00337% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00297%

Overall 0.00373% 45/1,207,725 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00705%	14,185
European (non-Finnish)	0.00448%	22,334
Remaining individualsnot grpmax-eligible	0.0021%	47,515

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: TEX11
Protein: p.Ile125Met
Coding: c.375C>G
MANE Select: NM_031276
Type: single nucleotide variant
Location: chrX:70853278 (GRCh38)
Structure: AlphaFold pLDDT 86.45

Full TEX11 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

TEX11 p.Ala871Val Uncertain significance ★ ⚠ same condition
TEX11 p.Ala98Ser Uncertain significance ★ ⚠ same condition
TEX11 p.Arg147Trp Uncertain significance ★ ⚠ same condition
TEX11 p.Arg474Gly Uncertain significance ★ ⚠ same condition
TEX11 p.Arg880Cys Uncertain significance ★ ⚠ same condition
TEX11 p.Asn325Lys Uncertain significance ★ ⚠ same condition
TEX11 p.Asn491Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
TEX11 p.Asn504Thr 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/tex11-p-ile125met (accessed [today's date]).

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