Is ATM p.Pro113Ser (c.337C>T) pathogenic?

ATM p.Pro113Ser (c.337C>T) is classified Uncertain significance in ATM (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.7467); Very rare (popmax 0.00134%, afr); Associated with hereditary breast carcinoma.

What condition is associated with ATM p.Pro113Ser (c.337C>T)?

ATM p.Pro113Ser (c.337C>T) is associated with hereditary breast carcinoma, ataxia telangiectasia, hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Pro113Ser (c.337C>T) in the general population?

ATM p.Pro113Ser (c.337C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Hereditary breast cancer inherited?

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

What do computational predictors say about ATM p.Pro113Ser (c.337C>T)?

AlphaMissense predicts likely pathogenic (score 0.7467) — an in-silico prediction, not a clinical call.

ATM p.Pro113Ser

c.337C>T · rs1060501678 · VCV407684

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.7467 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
AlphaMissense	0.7467	likely pathogenic
REVEL	0.483	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.75 · regional, not allelic
Overall
CADD	25.3	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 · 1/74,656 alleles

Overall 6.22e-05% 1/1,607,368 alleles · very rare exomes 0/1,455,262 · genomes 1/152,106 · joint denominator

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.Pro113Ser
Coding: c.337C>T
MANE Select: NM_000051
dbSNP: rs1060501678
Type: single nucleotide variant
Location: chr11:108235675 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 113: a UniProt-annotated variant site (in at)

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

Disease context

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

Also linked: ataxia telangiectasia hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

ATM p.Pro113Leu Uncertain significance ★★ same residue
ATM p.Pro113= Likely benign ★ same residue
ATM p.Pro113fs Pathogenic ★ 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

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-pro113ser (accessed [today's date]).

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