Is FES p.Val712Phe (c.2134G>T) pathogenic?

FES p.Val712Phe (c.2134G>T) is classified Uncertain significance in FES (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.2207); Absent from gnomAD v4.1.

How common is FES p.Val712Phe (c.2134G>T) in the general population?

FES p.Val712Phe (c.2134G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FES p.Val712Phe (c.2134G>T)?

AlphaMissense predicts likely benign (score 0.2207) — an in-silico prediction, not a clinical call.

FES p.Val712Phe

c.2134G>T · rs2033454157 · VCV3094486

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2207 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2207	likely benign
REVEL	0.347	indeterminate
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -5
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 9.3e-05 · regional, not allelic
Overall
CADD	17.15	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

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: FES
Protein: p.Val712Phe
Coding: c.2134G>T
MANE Select: NM_002005
dbSNP: rs2033454157
Type: single nucleotide variant
Location: chr15:90893742 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.63 · 12 PDB
Residue 712: the protein kinase domain; a β-strand

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

Similar variants

FES p.Ala588= Benign ★★ same type
FES p.Leu459= Benign ★★ same type
FES p.Met323Val Benign ★★ same type
FES p.Ala192Pro Uncertain significance ★ ⚠ same type
FES p.Ala22Asp Uncertain significance ★ ⚠ same type
FES p.Ala243Val Uncertain significance ★ ⚠ same type
FES p.Ala370Val Uncertain significance ★ ⚠ same type
FES p.Ala45Pro 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/fes-p-val712phe (accessed [today's date]).

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