Is ATM p.Pro80Ser (c.238C>T) pathogenic?

ATM p.Pro80Ser (c.238C>T) is classified Conflicting classifications of pathogenicity in ATM (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-01-06). AlphaMissense: likely benign (0.0996); Very rare (popmax 0.00134%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Pro80Ser (c.238C>T)?

ATM p.Pro80Ser (c.238C>T) is associated with hereditary neoplastic syndrome, ataxia telangiectasia, hereditary breast carcinoma (ClinVar).

How common is ATM p.Pro80Ser (c.238C>T) in the general population?

ATM p.Pro80Ser (c.238C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ATM p.Pro80Ser (c.238C>T)?

AlphaMissense predicts likely benign (score 0.0996) — an in-silico prediction, not a clinical call.

ATM p.Pro80Ser

c.238C>T · rs750597831 · VCV232904

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0996 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0996	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.008	GERP -1.2, phastCons 0.81
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.75 · regional, not allelic
Overall
CADD	13.55	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,824 alleles

Overall 0.000124% 2/1,613,108 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,824
European (non-Finnish)	8.48e-05%	1,179,614

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: ATM
Protein: p.Pro80Ser
Coding: c.238C>T
MANE Select: NM_000051
dbSNP: rs750597831
Type: single nucleotide variant
Location: chr11:108229230 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 80: a UniProt-annotated variant site (in at)

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ataxia telangiectasia hereditary breast carcinoma

Similar variants

ATM p.Pro80Leu Uncertain significance ★★ ⚠ same residue
ATM p.Pro80Thr Uncertain significance ★★ ⚠ same residue
ATM c.1607+1G>T Pathogenic ★★★ same condition
ATM c.2251-4A>G Likely pathogenic ★★★ same condition
ATM c.2466+5G>C Likely pathogenic ★★★ same condition
ATM c.3078-1G>A Pathogenic ★★★ same condition
ATM c.332-1G>A Pathogenic ★★★ same condition
ATM c.4909+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/atm-p-pro80ser (accessed [today's date]).

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