Is ATM p.Ser712Ter (c.2135C>A) pathogenic?

ATM p.Ser712Ter (c.2135C>A) is classified Pathogenic/Likely pathogenic in ATM (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-04-01). Absent from gnomAD v4.1; Associated with ataxia telangiectasia.

What condition is associated with ATM p.Ser712Ter (c.2135C>A)?

ATM p.Ser712Ter (c.2135C>A) is associated with ataxia telangiectasia, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is ATM p.Ser712Ter (c.2135C>A) in the general population?

ATM p.Ser712Ter (c.2135C>A) 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.

ATM p.Ser712Ter

c.2135C>A · rs1057516620 · VCV2735743

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ataxia telangiectasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 14 of 63
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -1.1, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Ser712Ter
Coding: c.2135C>A
MANE Select: NM_000051
dbSNP: rs1057516620
Type: single nucleotide variant
Location: chr11:108256225 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 712: 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 neoplastic syndrome hereditary breast carcinoma

For Ataxia-telangiectasia (Orphanet):

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

Similar variants

ATM p.Ser712Ala Uncertain significance ★★ ⚠ same residue
ATM p.Ser712Pro Uncertain significance ★★ ⚠ same residue
ATM p.Ser712Thr Uncertain significance ★★ ⚠ same residue
ATM p.Ser712Leu Uncertain significance ★ ⚠ same residue
ATM p.Ser712= Likely benign ★ same residue
ATM p.Ser712fs Pathogenic ★ same residue
ATM p.Ser712_Glu713insAsnSer Uncertain significance ★ same residue
ATM c.1607+1G>T 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-ser712ter (accessed [today's date]).

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