Is ANK1 p.Asn613Lys (c.1839C>G) pathogenic?

ANK1 p.Asn613Lys (c.1839C>G) is classified Uncertain significance in ANK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-27). AlphaMissense: ambiguous (0.4979); Ultra-rare (popmax 0.0165%, mid).

How common is ANK1 p.Asn613Lys (c.1839C>G) in the general population?

ANK1 p.Asn613Lys (c.1839C>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ANK1 p.Asn613Lys (c.1839C>G)?

AlphaMissense predicts ambiguous (score 0.4979) — an in-silico prediction, not a clinical call.

ANK1 p.Asn613Lys

c.1839C>G · rs141134967 · VCV1163298

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4979 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4979	ambiguous
REVEL	0.28	benign-leaning
SaProt	LLR -11.76	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.071, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 38 kb · p 1e-12 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,056 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,818 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,056
European (non-Finnish)	0.000169%	590,012

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: ANK1
Protein: p.Asn613Lys
Coding: c.1839C>G
MANE Select: NM_000037
dbSNP: rs141134967
Type: single nucleotide variant
Location: chr8:41708937 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 613: the '89 kda domain' region

Full ANK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANK1 c.1305+1G>A Pathogenic ★★ same type
ANK1 c.1405-9G>A Pathogenic/Likely pathogenic ★★ same type
ANK1 c.1702-2A>G Pathogenic/Likely pathogenic ★★ same type
ANK1 c.1801-17G>A Pathogenic/Likely pathogenic ★★ same type
ANK1 c.1801-2A>T Likely pathogenic ★★ same type
ANK1 c.1998+1G>T Likely pathogenic ★★ same type
ANK1 c.2296-1G>A Likely pathogenic ★★ same type
ANK1 c.2296-2A>G Pathogenic/Likely pathogenic ★★ same type

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/ank1-p-asn613lys (accessed [today's date]).

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