Is TP73 p.Arg348Gln (c.1043G>A) pathogenic?

TP73 p.Arg348Gln (c.1043G>A) is classified Uncertain significance in TP73 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.3); Ultra-rare (popmax 0.0183%, amr); Associated with Inborn genetic diseases.

What condition is associated with TP73 p.Arg348Gln (c.1043G>A)?

TP73 p.Arg348Gln (c.1043G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TP73 p.Arg348Gln (c.1043G>A) in the general population?

TP73 p.Arg348Gln (c.1043G>A) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about TP73 p.Arg348Gln (c.1043G>A)?

AlphaMissense predicts likely benign (score 0.3) — an in-silico prediction, not a clinical call.

TP73 p.Arg348Gln

c.1043G>A · VCV4189352

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3	likely benign
REVEL	0.652	pathogenic-leaning
SaProt	LLR -8.30	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 5,880 bp · p 0.0021 · regional, not allelic
Overall
CADD	26.9	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 0.0183% Admixed American · 11/59,988 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.00168% 27/1,611,882 alleles · ultra-rare exomes 23/1,459,668 · genomes 4/152,214 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,453
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
South Asian	0.0022%	45,542
European (non-Finnish)	0.0011%	90,766

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.Arg348Gln
Coding: c.1043G>A
MANE Select: NM_005427
Type: single nucleotide variant
Location: chr1:3728186 (GRCh38)
Gene constraint: LOEUF 0.576 · pLI 0.29 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.25 · 28 PDB
Residue 348: a UniProt-annotated variant site (in cild47); the 'oligomerization' region; the 'interaction with hipk2' region

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-arg348gln (accessed [today's date]).

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