Is TEX264 p.Pro41Ser (c.121C>T) pathogenic?

TEX264 p.Pro41Ser (c.121C>T) is classified Uncertain significance in TEX264 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-07). AlphaMissense: likely benign (0.2725); Ultra-rare (popmax 0.04%, amr).

How common is TEX264 p.Pro41Ser (c.121C>T) in the general population?

TEX264 p.Pro41Ser (c.121C>T) is ultra-rare (popmax 0.04%, amr) (gnomAD).

What do computational predictors say about TEX264 p.Pro41Ser (c.121C>T)?

AlphaMissense predicts likely benign (score 0.2725) — an in-silico prediction, not a clinical call.

TEX264 p.Pro41Ser

c.121C>T · rs199677902 · VCV2471071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2725 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.04%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2725	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -7.93	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 3.3	GERP 1.3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 30 kb · p 0.00092 · regional, not allelic
Overall
CADD	18.58	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 0.04% Admixed American · 24/60,024 alleles

Filtering AF 0.0275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0234%

Overall 0.00204% 33/1,614,196 alleles · ultra-rare exomes 15/1,461,868 · genomes 18/152,328 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.04%	2,501
East Asian	0.00223%	44,888
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)	0.000593%	168,577

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: TEX264
Protein: p.Pro41Ser
Coding: c.121C>T
MANE Select: NM_015926
dbSNP: rs199677902
Type: single nucleotide variant
Location: chr3:51674425 (GRCh38)
Gene constraint: LOEUF 0.798 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 76.05 · 2 PDB

Full TEX264 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TEX264 p.Ala127Ser Uncertain significance ★★ ⚠ same type
TEX264 p.Ala208Thr Uncertain significance ★ ⚠ same type
TEX264 p.Ala25Thr Uncertain significance ★ ⚠ same type
TEX264 p.Ala78Thr Uncertain significance ★ same type
TEX264 p.Ala95Ser Uncertain significance ★ ⚠ same type
TEX264 p.Arg162Gln Uncertain significance ★ ⚠ same type
TEX264 p.Arg162Trp Uncertain significance ★ ⚠ same type
TEX264 p.Arg186Gln Uncertain significance ★ ⚠ 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/tex264-p-pro41ser (accessed [today's date]).

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