Is ATM p.Ser707Pro (c.2119T>C) pathogenic?

ATM p.Ser707Pro (c.2119T>C) is classified Benign/Likely benign in ATM (ClinVar, Multiple submitters, 33 submitters; last evaluated 2026-07-01). AlphaMissense: likely benign (0.0804); Low-frequency (popmax 1.28%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Ser707Pro (c.2119T>C)?

ATM p.Ser707Pro (c.2119T>C) is associated with hereditary neoplastic syndrome, ataxia telangiectasia, hereditary breast carcinoma (ClinVar).

How common is ATM p.Ser707Pro (c.2119T>C) in the general population?

ATM p.Ser707Pro (c.2119T>C) is low-frequency (popmax 1.28%, nfe) (gnomAD).

What do computational predictors say about ATM p.Ser707Pro (c.2119T>C)?

AlphaMissense predicts likely benign (score 0.0804) — an in-silico prediction, not a clinical call.

ATM p.Ser707Pro

c.2119T>C · rs4986761 · VCV128454

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 33 submitters

AlphaMissense

likely benign

0.0804 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.28%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0804	likely benign
REVEL	0.249	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 -0.035	GERP 0.091
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.75 · regional, not allelic
Overall
CADD	11.04	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 1.28% European (non-Finnish) · 15,073/1,179,718 alleles

Filtering AF 1.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.25%

Overall 1.07% 17,270/1,613,392 alleles · low-frequency exomes 16,108/1,461,140 · genomes 1,162/152,252 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.28%	78
Middle Eastern	1.02%	98
Remaining individualsnot grpmax-eligible	0.866%	116
Ashkenazi Jewishnot grpmax-eligible	0.838%	119
Admixed American	0.708%	141
Finnishnot grpmax-eligible	0.547%	183
South Asian	0.466%	215
Amishnot grpmax-eligible	0.219%	456
African / African-American	0.192%	521
East Asian	0.00669%	14,948

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.Ser707Pro
Coding: c.2119T>C
MANE Select: NM_000051
dbSNP: rs4986761
Type: single nucleotide variant
Location: chr11:108254034 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 707: a UniProt-annotated variant site (in at); a turn; a UniProt-annotated variant site (in at; uncertain significance); a UniProt-annotated variant site (in)

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.Ser707Phe Uncertain significance ★ ⚠ same residue
ATM p.Ser707= Likely benign ★ same residue
ATM p.Ser707Thr Likely benign ★ same residue
ATM p.Ser707fs 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

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-ser707pro (accessed [today's date]).

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