Is ATM p.Val4Ala (c.11T>C) pathogenic?

ATM p.Val4Ala (c.11T>C) is classified Conflicting classifications of pathogenicity in ATM (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2022-01-12). AlphaMissense: likely benign (0.0457); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Val4Ala (c.11T>C)?

ATM p.Val4Ala (c.11T>C) is associated with hereditary neoplastic syndrome, ataxia telangiectasia (ClinVar).

How common is ATM p.Val4Ala (c.11T>C) in the general population?

ATM p.Val4Ala (c.11T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATM p.Val4Ala (c.11T>C)?

AlphaMissense predicts likely benign (score 0.0457) — an in-silico prediction, not a clinical call.

ATM p.Val4Ala

c.11T>C · rs1555053873 · VCV453356

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0457 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0457	likely benign
REVEL	0.109	moderately 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 1.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.75 · regional, not allelic
Overall
CADD	14.02	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

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.Val4Ala
Coding: c.11T>C
MANE Select: NM_000051
dbSNP: rs1555053873
Type: single nucleotide variant
Location: chr11:108227635 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)

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.Val4Leu Uncertain significance ★★ ⚠ same residue
ATM p.Val4Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
ATM p.Val4= Likely benign ★ 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

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-val4ala (accessed [today's date]).

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