Is ANK2 p.Asp3185= (c.9555C>T) pathogenic?

ANK2 p.Asp3185= (c.9555C>T) is classified Likely benign in ANK2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-15). Very rare (popmax 0.00439%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Asp3185= (c.9555C>T)?

ANK2 p.Asp3185= (c.9555C>T) is associated with Cardiovascular phenotype, long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Asp3185= (c.9555C>T) in the general population?

ANK2 p.Asp3185= (c.9555C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

ANK2 p.Asp3185=

c.9555C>T · rs371509239 · VCV413974

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.78	GERP -0.58, phastCons 0.27
Overall
CADD	6.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,088 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00161% 26/1,613,902 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,772
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
European (non-Finnish)	0.00161%	62,103
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00134%	74,900

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: ANK2
Protein: p.Asp3185=
Coding: c.9555C>T
MANE Select: NM_001148
dbSNP: rs371509239
Type: single nucleotide variant
Location: chr4:113358173 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3185: the 'disordered' region

Full ANK2 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: long QT syndrome cardiac arrhythmia, ankyrin-B-related

Similar variants

ANK2 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg1088Ter Pathogenic ★★ same condition
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg977Ter Pathogenic ★★ same condition
ANK2 c.11032+11G>T Uncertain significance ★★ same condition
ANK2 c.11611-3T>A Uncertain significance ★★ same condition
ANK2 c.1783-3C>T 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/ank2-p-asp3185 (accessed [today's date]).

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