Is TES p.Phe329Leu (c.985T>C) pathogenic?

TES p.Phe329Leu (c.985T>C) is classified Uncertain significance in TES (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: likely pathogenic (0.9665); Absent from gnomAD v4.1.

How common is TES p.Phe329Leu (c.985T>C) in the general population?

TES p.Phe329Leu (c.985T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TES p.Phe329Leu (c.985T>C)?

AlphaMissense predicts likely pathogenic (score 0.9665) — an in-silico prediction, not a clinical call.

TES p.Phe329Leu

c.985T>C · VCV3805812

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9665 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9665	likely pathogenic
REVEL	0.561	indeterminate
SaProt	LLR -8.17	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 47 kb · p 0.022 · regional, not allelic
Overall
CADD	23.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TES
Protein: p.Phe329Leu
Coding: c.985T>C
MANE Select: NM_015641
Type: single nucleotide variant
Location: chr7:116252384 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.97 · 2 PDB
Residue 329: a turn; the lim zinc-binding 2 domain

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-phe329leu (accessed [today's date]).

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