Is TP73 p.Ala336= (c.1008C>T) pathogenic?

TP73 p.Ala336= (c.1008C>T) is classified Benign in TP73 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-06-20). Common (popmax 17.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with TP73-related disorder.

What condition is associated with TP73 p.Ala336= (c.1008C>T)?

TP73 p.Ala336= (c.1008C>T) is associated with TP73-related disorder (ClinVar).

TP73 p.Ala336=

Q: How common is TP73 p.Ala336= (c.1008C>T) in the general population?

TP73 p.Ala336= (c.1008C>T) is common (popmax 17.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1008C>T · rs12046074 · VCV3056552

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 17.4%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

TP73-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.005	GERP -2.2, phastCons 0.014
Overall
CADD	7.709	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.4% East Asian · 7,799/44,838 alleles

Filtering AF 17.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.9%

Overall 4.27% 68,801/1,611,290 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	17.4%	6
Amishnot grpmax-eligible	9.21%	11
African / African-American	6.6%	15
Finnishnot grpmax-eligible	5.55%	18
Ashkenazi Jewishnot grpmax-eligible	5.41%	18
Remaining individualsnot grpmax-eligible	5.35%	19
Middle Eastern	4.74%	21
European (non-Finnish)	3.71%	27
South Asian	2.43%	41
Admixed American	2.2%	45

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.Ala336=
Coding: c.1008C>T
MANE Select: NM_005427
dbSNP: rs12046074
Type: single nucleotide variant
Location: chr1:3728151 (GRCh38)
Gene constraint: LOEUF 0.576 · pLI 0.29 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.25 · 28 PDB
Residue 336: a UniProt-annotated variant site (in cild47); the 'disordered' region

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

Disease context

TP73-related disorder

Similar variants

TP73 p.His349= Benign same condition
TP73 p.Ile626Val Likely benign same condition
TP73 p.Val586Met Likely benign ⚠ same condition
TP73 p.Arg538Cys Uncertain significance ★★ ⚠ same type
TP73 p.Gly451Arg Uncertain significance ★★ ⚠ same type
TP73 c.65+9G>A Benign/Likely benign ★★ same type
TP73 p.Ala325Thr Benign ★★ same type
TP73 p.Gln391= Benign ★★ 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/tp73-p-ala336 (accessed [today's date]).

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