Is ATM p.Ser1981= (c.5943C>T) pathogenic?

ATM p.Ser1981= (c.5943C>T) is classified Benign/Likely benign in ATM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-28). Very rare (popmax 0.00221%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with ATM p.Ser1981= (c.5943C>T)?

ATM p.Ser1981= (c.5943C>T) is associated with hereditary neoplastic syndrome, ataxia telangiectasia, hereditary breast carcinoma (ClinVar).

How common is ATM p.Ser1981= (c.5943C>T) in the general population?

ATM p.Ser1981= (c.5943C>T) is very rare (popmax 0.00221%, sas) (gnomAD).

ATM p.Ser1981=

c.5943C>T · rs769252226 · VCV232496

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

Conditions

hereditary neoplastic syndrome

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.21	loss · gain 0.01 · independent
Constraint at this position
Conservation	phyloP 1.7	GERP 1.7, phastCons 1
Overall
CADD	10.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% South Asian · 2/90,700 alleles

Filtering AF 0.000366% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000125% 2/1,596,180 alleles · very rare exomes 2/1,444,126 · genomes 0/152,054 · joint denominator

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.Ser1981=
Coding: c.5943C>T
MANE Select: NM_000051
dbSNP: rs769252226
Type: single nucleotide variant
Location: chr11:108312435 (GRCh38)

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 hereditary breast carcinoma

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-ser1981 (accessed [today's date]).

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