Is ATM p.Ser160Phe (c.479C>T) pathogenic?

ATM p.Ser160Phe (c.479C>T) is classified Uncertain significance in ATM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-29). AlphaMissense: ambiguous (0.3677); Very rare (popmax 0.000254%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Ser160Phe (c.479C>T)?

ATM p.Ser160Phe (c.479C>T) is associated with hereditary neoplastic syndrome, ataxia telangiectasia (ClinVar).

How common is ATM p.Ser160Phe (c.479C>T) in the general population?

ATM p.Ser160Phe (c.479C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about ATM p.Ser160Phe (c.479C>T)?

AlphaMissense predicts ambiguous (score 0.3677) — an in-silico prediction, not a clinical call.

ATM p.Ser160Phe

c.479C>T · rs35858242 · VCV232188

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3677 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.3677	ambiguous
REVEL	0.196	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.75 · regional, not allelic
Overall
CADD	26.1	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 0.000254% European (non-Finnish) · 3/1,179,820 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,498 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.Ser160Phe
Coding: c.479C>T
MANE Select: NM_000051
dbSNP: rs35858242
Type: single nucleotide variant
Location: chr11:108235817 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 160: 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

Similar variants

ATM p.Ser160Ala Uncertain significance ★★ ⚠ same residue
ATM p.Ser160Pro Uncertain significance ★★ ⚠ same residue
ATM p.Ser160= Likely benign ★ same residue
ATM p.Ser160fs Pathogenic/Likely pathogenic ★★ same residue
ATM p.Ser160_Gln161insHis 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

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-ser160phe (accessed [today's date]).

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