Is TEX11 p.Pro246Ser (c.736C>T) pathogenic?

TEX11 p.Pro246Ser (c.736C>T) is classified Likely benign in TEX11 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-05-20). AlphaMissense: likely benign (0.094); Ultra-rare (popmax 0.0975%, sas); Associated with TEX11-related disorder.

What condition is associated with TEX11 p.Pro246Ser (c.736C>T)?

TEX11 p.Pro246Ser (c.736C>T) is associated with TEX11-related disorder (ClinVar).

How common is TEX11 p.Pro246Ser (c.736C>T) in the general population?

TEX11 p.Pro246Ser (c.736C>T) is ultra-rare (popmax 0.0975%, sas) (gnomAD).

What do computational predictors say about TEX11 p.Pro246Ser (c.736C>T)?

AlphaMissense predicts likely benign (score 0.094) — an in-silico prediction, not a clinical call.

TEX11 p.Pro246Ser

c.736C>T · rs775098071 · VCV3054251

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.094 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0975%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TEX11-related disorder

Computational evidence

Protein change
AlphaMissense	0.094	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -7.17	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 2.8	GERP 0.17, phastCons 0.52
Regional constraint	o/e 0.83	unconstrained · MANE · 379 kb · p 2e-05 · regional, not allelic
Overall
CADD	8.957	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P261S vs ClinVar P246S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0975% South Asian · 31/31,806 alleles

Filtering AF 0.0705% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0614%

Overall 0.00306% 32/1,045,875 alleles · ultra-rare exomes 30/938,910 · genomes 2/106,965 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0975%	1,026
East Asian	0.0037%	27,030

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.Pro246Ser
Coding: c.736C>T
MANE Select: NM_031276
dbSNP: rs775098071
Type: single nucleotide variant
Location: chrX:70744176 (GRCh38)
Structure: AlphaFold pLDDT 86.45

Full TEX11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TEX11-related disorder

Similar variants

TEX11 c.38-7A>C Likely benign same condition
TEX11 p.Ala815= Likely benign same condition
TEX11 p.Asp832= Benign same condition
TEX11 p.Glu436Lys Benign same condition
TEX11 p.Ser816= Likely benign same condition
TEX11 c.1157-4dup Likely benign same condition
TEX11 c.1484-4T>C Likely benign ★★ same type
TEX11 p.Ala135= Benign/Likely 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/tex11-p-pro246ser (accessed [today's date]).

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