Is TEX10 p.Ser549Pro (c.1645T>C) pathogenic?

TEX10 p.Ser549Pro (c.1645T>C) is classified Uncertain significance in TEX10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: ambiguous (0.5221); Very rare (popmax 0.00134%, afr).

How common is TEX10 p.Ser549Pro (c.1645T>C) in the general population?

TEX10 p.Ser549Pro (c.1645T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about TEX10 p.Ser549Pro (c.1645T>C)?

AlphaMissense predicts ambiguous (score 0.5221) — an in-silico prediction, not a clinical call.

TEX10 p.Ser549Pro

c.1645T>C · VCV4183080

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5221 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5221	ambiguous
REVEL	0.11	moderately benign-leaning
SaProt	LLR -12.26	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 45 kb · p 9e-05 · regional, not allelic
Overall
CADD	23.9	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 0.00134% African / African-American · 1/74,664 alleles

Filtering AF 0.000436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000318%

Overall 0.000694% 11/1,585,126 alleles · very rare exomes 8/1,432,956 · genomes 3/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,664
European (non-Finnish)	0.000861%	116,120

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: TEX10
Protein: p.Ser549Pro
Coding: c.1645T>C
MANE Select: NM_017746
Type: single nucleotide variant
Location: chr9:100327943 (GRCh38)
Gene constraint: LOEUF 0.35 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.04 · 4 PDB
Residue 549: an α-helix

Full TEX10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TEX10 p.Ala112Thr Uncertain significance ★ ⚠ same type
TEX10 p.Ala273Thr Uncertain significance ★ ⚠ same type
TEX10 p.Ala651Thr Uncertain significance ★ ⚠ same type
TEX10 p.Arg178His Uncertain significance ★ ⚠ same type
TEX10 p.Arg350Gln Uncertain significance ★ ⚠ same type
TEX10 p.Arg550Cys Uncertain significance ★ ⚠ same type
TEX10 p.Arg703Gln Uncertain significance ★ ⚠ same type
TEX10 p.Arg7Cys 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/tex10-p-ser549pro (accessed [today's date]).

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