Is ATM p.Phe570Ser (c.1709T>C) pathogenic?

ATM p.Phe570Ser (c.1709T>C) is classified Uncertain significance in ATM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-17). AlphaMissense: likely benign (0.1013); Very rare (popmax 0.00017%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Phe570Ser (c.1709T>C)?

ATM p.Phe570Ser (c.1709T>C) is associated with hereditary neoplastic syndrome, ataxia telangiectasia (ClinVar).

How common is ATM p.Phe570Ser (c.1709T>C) in the general population?

ATM p.Phe570Ser (c.1709T>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about ATM p.Phe570Ser (c.1709T>C)?

AlphaMissense predicts likely benign (score 0.1013) — an in-silico prediction, not a clinical call.

ATM p.Phe570Ser

c.1709T>C · rs777301065 · VCV661564

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1013 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1013	likely benign
REVEL	0.291	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -0.21, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.75 · regional, not allelic
Overall
CADD	16.32	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 0.00017% European (non-Finnish) · 2/1,179,810 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,574 alleles · very rare

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.Phe570Ser
Coding: c.1709T>C
MANE Select: NM_000051
dbSNP: rs777301065
Type: single nucleotide variant
Location: chr11:108251938 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 570: a UniProt-annotated variant site (in at); 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

Also linked: ataxia telangiectasia

Similar variants

ATM p.Phe570Ile Uncertain significance ★★ ⚠ same residue
ATM p.Phe570Val 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-phe570ser (accessed [today's date]).

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