Is ANK2 p.Pro1950His (c.5849C>A) pathogenic?

ANK2 p.Pro1950His (c.5849C>A) is classified Uncertain significance in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-02). AlphaMissense: likely benign (0.1008); Very rare (popmax 0.005%, amr); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Pro1950His (c.5849C>A)?

ANK2 p.Pro1950His (c.5849C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is ANK2 p.Pro1950His (c.5849C>A) in the general population?

ANK2 p.Pro1950His (c.5849C>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ANK2 p.Pro1950His (c.5849C>A)?

AlphaMissense predicts likely benign (score 0.1008) — an in-silico prediction, not a clinical call.

ANK2 p.Pro1950His

c.5849C>A · rs1241451043 · VCV1750047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1008 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1008	likely benign
REVEL	0.187	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP 1.7, phastCons 0.006
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	19.67	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,002 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,614,004 alleles · very rare exomes 0/1,461,838 · genomes 3/152,166 · 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: ANK2
Protein: p.Pro1950His
Coding: c.5849C>A
MANE Select: NM_001148
dbSNP: rs1241451043
Type: single nucleotide variant
Location: chr4:113354467 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1950: the 'disordered' region; the 'repeat-rich region' 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

Similar variants

ANK2 p.Pro1950= Likely benign ★ same residue
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg977Ter Pathogenic ★★ same condition
ANK2 c.11611-3T>A Uncertain significance ★★ same condition
ANK2 c.1783-3C>T Uncertain significance ★★ same condition
ANK2 c.2079+5T>G Uncertain significance ★★ same condition
ANK2 p.Ala1152Val 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-pro1950his (accessed [today's date]).

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