Is TP53 p.Ser362Asn (c.1085G>A) pathogenic?

TP53 p.Ser362Asn (c.1085G>A) is classified Conflicting classifications of pathogenicity in TP53 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-07). AlphaMissense: likely benign (0.0808); Very rare (popmax 0.0011%, sas); Associated with Li-Fraumeni syndrome.

What condition is associated with TP53 p.Ser362Asn (c.1085G>A)?

TP53 p.Ser362Asn (c.1085G>A) is associated with Li-Fraumeni syndrome, hereditary neoplastic syndrome (ClinVar).

How common is TP53 p.Ser362Asn (c.1085G>A) in the general population?

TP53 p.Ser362Asn (c.1085G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Li-Fraumeni syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about TP53 p.Ser362Asn (c.1085G>A)?

AlphaMissense predicts likely benign (score 0.0808) — an in-silico prediction, not a clinical call.

TP53 p.Ser362Asn

c.1085G>A · rs768803947 · VCV458516

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0808 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Li-Fraumeni syndrome

Computational evidence

Protein change
AlphaMissense	0.0808	likely benign
REVEL	0.345	indeterminate
SaProt	LLR -8.28	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.061	GERP -2.6, phastCons 0.81
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	6.736	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 0.0011% South Asian · 1/90,978 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000806% 13/1,613,352 alleles · very rare exomes 13/1,461,040 · genomes 0/152,312 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,978
European (non-Finnish)	0.00102%	98,288

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: TP53
Protein: p.Ser362Asn
Coding: c.1085G>A
MANE Select: NM_000546
dbSNP: rs768803947
Type: single nucleotide variant
Location: chr17:7670624 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 362: the 'interaction with carm1' region; the 'disordered' region; the 'interaction with usp7' region; the 'interaction with hipk1' region

Full TP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Li-Fraumeni syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Li-Fraumeni syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (United Kingdom)

Similar variants

TP53 p.Ser362Gly Uncertain significance ★★ ⚠ same residue
TP53 p.Ser362Arg Uncertain significance ★ ⚠ same residue
TP53 p.Ser362Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ser362Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ser362fs Pathogenic/Likely pathogenic ★★ same residue
TP53 c.375+5G>A Likely pathogenic ★★★ same condition
TP53 c.919+1G>A Pathogenic ★★★ same condition
TP53 c.97-1G>A Pathogenic ★★★ 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/tp53-p-ser362asn (accessed [today's date]).

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