Is TES p.Leu55Phe (c.165G>C) pathogenic?

TES p.Leu55Phe (c.165G>C) is classified Uncertain significance in TES (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-05). AlphaMissense: likely benign (0.0882); Very rare (popmax 0.000593%, nfe).

How common is TES p.Leu55Phe (c.165G>C) in the general population?

TES p.Leu55Phe (c.165G>C) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about TES p.Leu55Phe (c.165G>C)?

AlphaMissense predicts likely benign (score 0.0882) — an in-silico prediction, not a clinical call.

TES p.Leu55Phe

c.165G>C · rs367601028 · VCV3176164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0882 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0882	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -5.54	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 1.5	GERP -1.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 47 kb · p 0.022 · regional, not allelic
Overall
CADD	16.01	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 0.000593% European (non-Finnish) · 7/1,179,804 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,676 alleles · very rare exomes 6/1,461,558 · genomes 1/152,118 · joint denominator

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.Leu55Phe
Coding: c.165G>C
MANE Select: NM_015641
dbSNP: rs367601028
Type: single nucleotide variant
Location: chr7:116249071 (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-leu55phe (accessed [today's date]).

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