Is ATM p.Ser751Pro (c.2251T>C) pathogenic?

ATM p.Ser751Pro (c.2251T>C) is classified Uncertain significance in ATM (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-20). AlphaMissense: likely pathogenic (0.6038); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Ser751Pro (c.2251T>C)?

ATM p.Ser751Pro (c.2251T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Ser751Pro (c.2251T>C) in the general population?

ATM p.Ser751Pro (c.2251T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATM p.Ser751Pro (c.2251T>C)?

AlphaMissense predicts likely pathogenic (score 0.6038) — an in-silico prediction, not a clinical call.

ATM p.Ser751Pro

c.2251T>C · rs1064793558 · VCV1788447

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6038 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.6038	likely pathogenic
REVEL	0.371	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.32	acceptor loss, 19 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5.1	GERP 2.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.75 · regional, not allelic
Overall
CADD	24.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATM
Protein: p.Ser751Pro
Coding: c.2251T>C
MANE Select: NM_000051
dbSNP: rs1064793558
Type: single nucleotide variant
Location: chr11:108257481 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 751: a UniProt-annotated variant site (in at); an α-helix; a UniProt-annotated variant site (in at; uncertain significance)

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

Similar variants

ATM p.Ser751Thr Uncertain significance ★★ ⚠ same residue
ATM p.Ser751Cys Uncertain significance ★ same residue
ATM p.Ser751= Likely benign ★ 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-ser751pro (accessed [today's date]).

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