Is ATM p.Val682Phe (c.2044G>T) pathogenic?

ATM p.Val682Phe (c.2044G>T) is classified Uncertain significance in ATM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-03). AlphaMissense: likely benign (0.1735); Very rare (popmax 0.000424%, nfe); Associated with ataxia telangiectasia.

What condition is associated with ATM p.Val682Phe (c.2044G>T)?

ATM p.Val682Phe (c.2044G>T) is associated with ataxia telangiectasia, hereditary breast carcinoma (ClinVar).

How common is ATM p.Val682Phe (c.2044G>T) in the general population?

ATM p.Val682Phe (c.2044G>T) is very rare (popmax 0.000424%, nfe) (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.Val682Phe (c.2044G>T)?

AlphaMissense predicts likely benign (score 0.1735) — an in-silico prediction, not a clinical call.

ATM p.Val682Phe

c.2044G>T · rs2135369797 · VCV1489968

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1735 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

ataxia telangiectasia

Computational evidence

Protein change
AlphaMissense	0.1735	likely benign
REVEL	0.333	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.32	acceptor gain · deltas
Pangolin	Δ0.33	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.75 · regional, not allelic
Overall
CADD	23.1	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

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,000 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,784 alleles · very rare

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.Val682Phe
Coding: c.2044G>T
MANE Select: NM_000051
dbSNP: rs2135369797
Type: single nucleotide variant
Location: chr11:108253959 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 682: a UniProt-annotated variant site (in at); 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 breast carcinoma

For Ataxia-telangiectasia (Orphanet):

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

Similar variants

ATM p.Val682Gly Uncertain significance ★★ same residue
ATM p.Val682Leu Uncertain significance ★★ ⚠ same residue
ATM p.Val682= Likely benign ★ same residue
ATM p.Val682fs Pathogenic ★★ same residue
ATM p.Val682Ala Uncertain significance ★ same residue
ATM p.Val682Ile Uncertain significance ★ ⚠ same residue
ATM c.1607+1G>T Pathogenic ★★★ same condition
ATM c.2251-4A>G Likely 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-val682phe (accessed [today's date]).

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