Is TP73 p.Gln207Pro (c.620A>C) pathogenic?

TP73 p.Gln207Pro (c.620A>C) is classified Uncertain significance in TP73 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely benign (0.1426); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with TP73 p.Gln207Pro (c.620A>C)?

TP73 p.Gln207Pro (c.620A>C) is associated with Inborn genetic diseases (ClinVar).

How common is TP73 p.Gln207Pro (c.620A>C) in the general population?

TP73 p.Gln207Pro (c.620A>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about TP73 p.Gln207Pro (c.620A>C)?

AlphaMissense predicts likely benign (score 0.1426) — an in-silico prediction, not a clinical call.

TP73 p.Gln207Pro

c.620A>C · VCV3460401

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1426 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1426	likely benign
REVEL	0.789	moderately pathogenic-leaning
SaProt	LLR -13.43	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.90	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 5,065 bp · p 3.9e-10 · regional, not allelic
Overall
CADD	25.6	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 0.00133% African / African-American · 1/74,922 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,612,134 alleles · very rare exomes 5/1,459,934 · genomes 2/152,200 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,440
African / African-Americangrpmax	0.00133%	74,922
European (non-Finnish)	0.000424%	235,913

Remaining individuals 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: TP73
Protein: p.Gln207Pro
Coding: c.620A>C
MANE Select: NM_005427
Type: single nucleotide variant
Location: chr1:3723357 (GRCh38)
Gene constraint: LOEUF 0.576 · pLI 0.29 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.25 · 28 PDB
Residue 207: a UniProt-annotated variant site (in cild47); the 'dna-binding' region; a β-strand

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-gln207pro (accessed [today's date]).

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