Is ATM p.Phe172Val (c.514T>G) pathogenic?

ATM p.Phe172Val (c.514T>G) is classified Uncertain significance in ATM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-30). AlphaMissense: likely benign (0.125); Absent from gnomAD v4.1; Associated with ataxia telangiectasia.

What condition is associated with ATM p.Phe172Val (c.514T>G)?

ATM p.Phe172Val (c.514T>G) is associated with ataxia telangiectasia (ClinVar).

How common is ATM p.Phe172Val (c.514T>G) in the general population?

ATM p.Phe172Val (c.514T>G) 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.Phe172Val (c.514T>G)?

AlphaMissense predicts likely benign (score 0.125) — an in-silico prediction, not a clinical call.

ATM p.Phe172Val

c.514T>G · rs786201608 · VCV2012558

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.125 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

ataxia telangiectasia

Computational evidence

Protein change
AlphaMissense	0.125	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	Δ0.66	acceptor loss, 5 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5	GERP -0.36, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.75 · regional, not allelic
Overall
CADD	18.61	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 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.Phe172Val
Coding: c.514T>G
MANE Select: NM_000051
dbSNP: rs786201608
Type: single nucleotide variant
Location: chr11:108243970 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 172: a UniProt-annotated variant site (in at); an α-helix

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

For Ataxia-telangiectasia (Orphanet):

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

Similar variants

ATM p.Phe172Leu Uncertain significance ★★ same residue
ATM p.Phe172= Conflicting classifications of pathogenicity ★ same residue
ATM p.Phe172Cys 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
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-phe172val (accessed [today's date]).

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