Is TEX10 p.Ser220Phe (c.659C>T) pathogenic?

TEX10 p.Ser220Phe (c.659C>T) is classified Uncertain significance in TEX10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-30). AlphaMissense: likely pathogenic (0.8961); Very rare (popmax 0.00364%, nfe).

How common is TEX10 p.Ser220Phe (c.659C>T) in the general population?

TEX10 p.Ser220Phe (c.659C>T) is very rare (popmax 0.00364%, nfe) (gnomAD).

What do computational predictors say about TEX10 p.Ser220Phe (c.659C>T)?

AlphaMissense predicts likely pathogenic (score 0.8961) — an in-silico prediction, not a clinical call.

TEX10 p.Ser220Phe

c.659C>T · rs751449521 · VCV2299280

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8961 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00364%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8961	likely pathogenic · top 10% in TEX10
REVEL	0.552	indeterminate
SaProt	LLR -11.10	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.24	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 45 kb · p 9e-05 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00364% European (non-Finnish) · 43/1,180,016 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00279% 45/1,614,184 alleles · very rare exomes 45/1,461,862 · genomes 0/152,322 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00364%	27,442
Remaining individualsnot grpmax-eligible	0.0032%	31,255

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.Ser220Phe
Coding: c.659C>T
MANE Select: NM_017746
dbSNP: rs751449521
Type: single nucleotide variant
Location: chr9:100346928 (GRCh38)
Gene constraint: LOEUF 0.35 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.04 · 4 PDB
Residue 220: 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-ser220phe (accessed [today's date]).

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