Is TP73 p.Ser117Phe (c.350C>T) pathogenic?

TP73 p.Ser117Phe (c.350C>T) is classified Uncertain significance in TP73 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). AlphaMissense: likely pathogenic (0.9836); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TP73 p.Ser117Phe (c.350C>T)?

TP73 p.Ser117Phe (c.350C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TP73 p.Ser117Phe (c.350C>T) in the general population?

TP73 p.Ser117Phe (c.350C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TP73 p.Ser117Phe (c.350C>T)?

AlphaMissense predicts likely pathogenic (score 0.9836) — an in-silico prediction, not a clinical call.

TP73 p.Ser117Phe

c.350C>T · rs2524664060 · VCV2555209

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9836 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9836	likely pathogenic
REVEL	0.961	strongly pathogenic-leaning
SaProt	LLR -13.22	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 40 kb · p 0.3 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: TP73
Protein: p.Ser117Phe
Coding: c.350C>T
MANE Select: NM_005427
dbSNP: rs2524664060
Type: single nucleotide variant
Location: chr1:3707712 (GRCh38)
Gene constraint: LOEUF 0.576 · pLI 0.29 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.25 · 28 PDB
Residue 117: an α-helix

Full TP73 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TP73 p.Gly451Arg Uncertain significance ★★ ⚠ same condition
TP73 p.Ala100Thr Uncertain significance ★ ⚠ same condition
TP73 p.Ala112Val Uncertain significance ★ ⚠ same condition
TP73 p.Ala156Thr Uncertain significance ★ ⚠ same condition
TP73 p.Ala320Thr Uncertain significance ★ ⚠ same condition
TP73 p.Ala441Pro Uncertain significance ★ ⚠ same condition
TP73 p.Ala441Thr Uncertain significance ★ ⚠ same condition
TP73 p.Ala459Val Uncertain significance ★ ⚠ same condition

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/tp73-p-ser117phe (accessed [today's date]).

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