Is TES p.Pro209Ser (c.625C>T) pathogenic?

TES p.Pro209Ser (c.625C>T) is classified Uncertain significance in TES (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.0676); Ultra-rare (popmax 0.0671%, amr).

How common is TES p.Pro209Ser (c.625C>T) in the general population?

TES p.Pro209Ser (c.625C>T) is ultra-rare (popmax 0.0671%, amr) (gnomAD).

What do computational predictors say about TES p.Pro209Ser (c.625C>T)?

AlphaMissense predicts likely benign (score 0.0676) — an in-silico prediction, not a clinical call.

TES p.Pro209Ser

c.625C>T · rs188977232 · VCV2268830

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0676 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0671%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0676	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -5.76	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 3.2	GERP 0.86, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 47 kb · p 0.022 · regional, not allelic
Overall
CADD	17.3	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 0.0671% Admixed American · 40/59,630 alleles

Filtering AF 0.0506% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0449%

Overall 0.0137% 221/1,611,216 alleles · ultra-rare exomes 191/1,458,900 · genomes 30/152,316 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0671%	1,491
Middle Eastern	0.0662%	1,511
Remaining individualsnot grpmax-eligible	0.0481%	2,079
African / African-American	0.0187%	5,356
European (non-Finnish)	0.0113%	8,862

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: TES
Protein: p.Pro209Ser
Coding: c.625C>T
MANE Select: NM_015641
dbSNP: rs188977232
Type: single nucleotide variant
Location: chr7:116250419 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.97 · 2 PDB

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

Similar variants

TES p.Ala186Val Uncertain significance ★ ⚠ same type
TES p.Ala227Thr Uncertain significance ★ ⚠ same type
TES p.Ala384Thr Uncertain significance ★ ⚠ same type
TES p.Ala77Thr Uncertain significance ★ ⚠ same type
TES p.Arg374Trp Uncertain significance ★ ⚠ same type
TES p.Arg89Cys Uncertain significance ★ ⚠ same type
TES p.Asn107Asp Uncertain significance ★ ⚠ same type
TES p.Asp345Tyr 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/tes-p-pro209ser (accessed [today's date]).

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