Is ATM p.Ser367Phe (c.1100C>T) pathogenic?

ATM p.Ser367Phe (c.1100C>T) is classified Conflicting classifications of pathogenicity in ATM (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-09). AlphaMissense: likely benign (0.2278); Absent from gnomAD v4.1; Associated with ataxia telangiectasia.

What condition is associated with ATM p.Ser367Phe (c.1100C>T)?

ATM p.Ser367Phe (c.1100C>T) is associated with ataxia telangiectasia, hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Ser367Phe (c.1100C>T) in the general population?

ATM p.Ser367Phe (c.1100C>T) is absent from gnomAD v4.1 (gnomAD).

How is Ataxia-telangiectasia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ATM p.Ser367Phe (c.1100C>T)?

AlphaMissense predicts likely benign (score 0.2278) — an in-silico prediction, not a clinical call.

ATM p.Ser367Phe

c.1100C>T · rs2079990831 · VCV1021081

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2278 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

ataxia telangiectasia

Computational evidence

Protein change
AlphaMissense	0.2278	likely benign
REVEL	0.092	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.75 · regional, not allelic
Overall
CADD	24.2	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

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.Ser367Phe
Coding: c.1100C>T
MANE Select: NM_000051
dbSNP: rs2079990831
Type: single nucleotide variant
Location: chr11:108248967 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 367: a modified residue (phosphoserine; by autocatalysis); a UniProt-annotated variant site (in at)

Full ATM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ataxia telangiectasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Ataxia-telangiectasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: 1-5 / 10 000 (Norway)

Similar variants

ATM p.Ser367Tyr Uncertain significance ★★ ⚠ same residue
ATM p.Ser367= Likely benign ★★ same residue
ATM p.Ser367Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
ATM p.Ser367fs 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-ser367phe (accessed [today's date]).

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