Is TES p.Glu33Val (c.98A>T) pathogenic?

TES p.Glu33Val (c.98A>T) is classified Uncertain significance in TES (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely pathogenic (0.7992); Very rare (popmax 0.00653%, nfe).

How common is TES p.Glu33Val (c.98A>T) in the general population?

TES p.Glu33Val (c.98A>T) is very rare (popmax 0.00653%, nfe) (gnomAD).

What do computational predictors say about TES p.Glu33Val (c.98A>T)?

AlphaMissense predicts likely pathogenic (score 0.7992) — an in-silico prediction, not a clinical call.

TES p.Glu33Val

c.98A>T · VCV4182828

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00653%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7992	likely pathogenic
REVEL	0.463	indeterminate
SaProt	LLR -7.91	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.3	GERP 1.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 47 kb · p 0.022 · regional, not allelic
Overall
CADD	28.3	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 0.00653% European (non-Finnish) · 77/1,179,812 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0049%

Overall 0.00613% 99/1,613,742 alleles · very rare exomes 88/1,461,518 · genomes 11/152,224 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0473%	2,114
Remaining individualsnot grpmax-eligible	0.0128%	7,807
European (non-Finnish)grpmax	0.00653%	15,322

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu33Val
Coding: c.98A>T
MANE Select: NM_015641
Type: single nucleotide variant
Location: chr7:116234604 (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-glu33val (accessed [today's date]).

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