Is ANK1 p.Ala565= (c.1695C>T) pathogenic?

ANK1 p.Ala565= (c.1695C>T) is classified Likely benign in ANK1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-18). Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with ANK1 p.Ala565= (c.1695C>T)?

ANK1 p.Ala565= (c.1695C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANK1 p.Ala565= (c.1695C>T) in the general population?

ANK1 p.Ala565= (c.1695C>T) is very rare (popmax 0.005%, amr) (gnomAD).

ANK1 p.Ala565=

c.1695C>T · rs987458909 · VCV2966556

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -4.3
Overall
CADD	0.072	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,988 alleles

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

Overall 0.000991% 16/1,613,882 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,996
European (non-Finnish)	0.0011%	90,770

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.Ala565=
Coding: c.1695C>T
MANE Select: NM_000037
dbSNP: rs987458909
Type: single nucleotide variant
Location: chr8:41714982 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 565: the '89 kda domain' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANK1 p.Ala565Ser Uncertain significance ★ ⚠ same residue
ANK1 p.Ala1590Thr Uncertain significance ★★ ⚠ same condition
ANK1 p.Ala1659Val Uncertain significance ★★ ⚠ same condition
ANK1 p.Ala1789Thr Uncertain significance ★★ ⚠ same condition
ANK1 p.Ala329Ser Uncertain significance ★★ ⚠ same condition
ANK1 p.Ala543Val Uncertain significance ★★ ⚠ same condition
ANK1 p.Arg1148Gln Uncertain significance ★★ ⚠ same condition
ANK1 p.Arg1255His 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/ank1-p-ala565 (accessed [today's date]).

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