Is ATM p.Cys987Phe (c.2960G>T) pathogenic?

ATM p.Cys987Phe (c.2960G>T) is classified Uncertain significance in ATM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-14). AlphaMissense: likely pathogenic (0.8115); No allele count reported in gnomAD v4.1 (AN 1,610,426); Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Cys987Phe (c.2960G>T)?

ATM p.Cys987Phe (c.2960G>T) is associated with hereditary neoplastic syndrome, ataxia telangiectasia (ClinVar).

How common is ATM p.Cys987Phe (c.2960G>T) in the general population?

ATM p.Cys987Phe (c.2960G>T) is no allele count reported in gnomAD v4.1 (AN 1,610,426) (gnomAD).

What do computational predictors say about ATM p.Cys987Phe (c.2960G>T)?

AlphaMissense predicts likely pathogenic (score 0.8115) — an in-silico prediction, not a clinical call.

ATM p.Cys987Phe

c.2960G>T · rs1555085052 · VCV1798166

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8115 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,610,426)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.8115	likely pathogenic
REVEL	0.812	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.75 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,610,426). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ATM
Protein: p.Cys987Phe
Coding: c.2960G>T
MANE Select: NM_000051
dbSNP: rs1555085052
Type: single nucleotide variant
Location: chr11:108271289 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 987: 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

Also linked: ataxia telangiectasia

Similar variants

ATM p.Cys987Gly Uncertain significance ★★ same residue
ATM p.Cys987Tyr Uncertain significance ★★ ⚠ same residue
ATM p.Cys987Trp Uncertain significance ★ ⚠ same residue
ATM p.Cys987Arg 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

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-cys987phe (accessed [today's date]).

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