Is TXK p.Phe13Ser (c.38T>C) pathogenic?

TXK p.Phe13Ser (c.38T>C) is classified Uncertain significance in TXK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: ambiguous (0.3409); Ultra-rare (popmax 0.0165%, sas).

How common is TXK p.Phe13Ser (c.38T>C) in the general population?

TXK p.Phe13Ser (c.38T>C) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

What do computational predictors say about TXK p.Phe13Ser (c.38T>C)?

AlphaMissense predicts ambiguous (score 0.3409) — an in-silico prediction, not a clinical call.

TXK p.Phe13Ser

c.38T>C · VCV3976240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3409 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3409	ambiguous
REVEL	0.196	benign-leaning
SaProt	LLR -6.99	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 7.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 67 kb · p 0.023 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/91,078 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.000929% 15/1,614,150 alleles · ultra-rare exomes 15/1,461,808 · genomes 0/152,342 · joint denominator

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: TXK
Protein: p.Phe13Ser
Coding: c.38T>C
MANE Select: NM_003328
Type: single nucleotide variant
Location: chr4:48114381 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.88 · 1 PDB

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

Similar variants

TXK p.Ala160Val Uncertain significance ★ ⚠ same type
TXK p.Ala172Ser Uncertain significance ★ ⚠ same type
TXK p.Ala192Val Uncertain significance ★ ⚠ same type
TXK p.Ala491Thr Uncertain significance ★ ⚠ same type
TXK p.Ala514Val Uncertain significance ★ ⚠ same type
TXK p.Ala519Thr Uncertain significance ★ ⚠ same type
TXK p.Ala524Glu Uncertain significance ★ ⚠ same type
TXK p.Arg241His 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/txk-p-phe13ser (accessed [today's date]).

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