Is ATM p.Val519Phe (c.1555G>T) pathogenic?

ATM p.Val519Phe (c.1555G>T) is classified Uncertain significance in ATM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-12). AlphaMissense: likely benign (0.1855); Very rare (popmax 0.00223%, eas); Associated with ataxia telangiectasia.

What condition is associated with ATM p.Val519Phe (c.1555G>T)?

ATM p.Val519Phe (c.1555G>T) is associated with ataxia telangiectasia, hereditary neoplastic syndrome (ClinVar).

How common is ATM p.Val519Phe (c.1555G>T) in the general population?

ATM p.Val519Phe (c.1555G>T) is very rare (popmax 0.00223%, eas) (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.Val519Phe (c.1555G>T)?

AlphaMissense predicts likely benign (score 0.1855) — an in-silico prediction, not a clinical call.

ATM p.Val519Phe

c.1555G>T · rs758056561 · VCV578905

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1855 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

ataxia telangiectasia

Computational evidence

Protein change
AlphaMissense	0.1855	likely benign
REVEL	0.09	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 0.43	GERP -2.9, phastCons 0.98
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.75 · regional, not allelic
Overall
CADD	9.029	PHRED · no single calibrated threshold — expert panels disagree

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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,886 alleles

Overall 0.000137% 2/1,461,862 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,886
European (non-Finnish)	8.47e-05%	1,180,025

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.Val519Phe
Coding: c.1555G>T
MANE Select: NM_000051
dbSNP: rs758056561
Type: single nucleotide variant
Location: chr11:108251020 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 519: 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

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.Val519Asp Uncertain significance ★★ same residue
ATM p.Val519Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
ATM p.Val519Ile Conflicting classifications of pathogenicity ★ ⚠ 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-val519phe (accessed [today's date]).

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