Is ANKRD1 p.Thr116= (c.348G>A) pathogenic?

ANKRD1 p.Thr116= (c.348G>A) is classified Benign in ANKRD1 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-03). Common (popmax 8.63%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with ANKRD1 p.Thr116= (c.348G>A)?

ANKRD1 p.Thr116= (c.348G>A) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy (ClinVar).

ANKRD1 p.Thr116=

Q: How common is ANKRD1 p.Thr116= (c.348G>A) in the general population?

ANKRD1 p.Thr116= (c.348G>A) is common (popmax 8.63%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.348G>A · rs137914723 · VCV45633

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 8.63%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.56	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -1.7	GERP -4.8
Overall
CADD	15.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.63% Admixed American · 4,912/56,920 alleles

Filtering AF 8.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.35%

Overall 0.379% 5,928/1,564,118 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	8.63%	12
East Asian	1.4%	72
Remaining individualsnot grpmax-eligible	0.35%	285
African / African-American	0.182%	551
South Asian	0.0279%	3,580
Middle Eastern	0.0169%	5,920
European (non-Finnish)	0.00648%	15,437
Finnishnot grpmax-eligible	0.00501%	19,957

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: ANKRD1
Protein: p.Thr116=
Coding: c.348G>A
MANE Select: NM_014391
dbSNP: rs137914723
Type: single nucleotide variant
Location: chr10:90918970 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.64
Residue 116: a UniProt-annotated variant site (found in a sporadic case of total anomalous pulmonary venous return; uncertain significance)

Full ANKRD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy dilated cardiomyopathy

Similar variants

ANKRD1 p.Thr116Met Conflicting classifications of pathogenicity ★ ⚠ same residue
ANKRD1 c.207+1G>T Uncertain significance ★★ same condition
ANKRD1 c.27+1G>T Uncertain significance ★★ same condition
ANKRD1 c.28-3T>C Uncertain significance ★★ same condition
ANKRD1 c.651+4T>A Uncertain significance ★★ same condition
ANKRD1 c.651+6C>T Uncertain significance ★★ same condition
ANKRD1 c.750+2T>C Uncertain significance ★★ same condition
ANKRD1 c.750+4A>G Uncertain significance ★★ 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/ankrd1-p-thr116 (accessed [today's date]).

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