Is ANK3 p.Leu3077= (c.9231C>T) pathogenic?

ANK3 p.Leu3077= (c.9231C>T) is classified Likely benign in ANK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). Ultra-rare (popmax 0.0156%, sas).

How common is ANK3 p.Leu3077= (c.9231C>T) in the general population?

ANK3 p.Leu3077= (c.9231C>T) is ultra-rare (popmax 0.0156%, sas) (gnomAD).

ANK3 p.Leu3077=

c.9231C>T · rs757578753 · VCV723887

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, sas)

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 -0.13	GERP -7.8
Overall
CADD	2.623	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% South Asian · 14/89,926 alleles

Filtering AF 0.00941% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00754%

Overall 0.0018% 29/1,608,564 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0156%	6,423
Remaining individualsnot grpmax-eligible	0.00804%	12,441
Admixed American	0.00169%	59,036
African / African-American	0.00134%	74,402
European (non-Finnish)	0.000679%	147,281

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: ANK3
Protein: p.Leu3077=
Coding: c.9231C>T
MANE Select: NM_020987
dbSNP: rs757578753
Type: single nucleotide variant
Location: chr10:60071650 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)

Full ANK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANK3 c.2382+6C>T Uncertain significance ★★ same type
ANK3 p.Ala1461Thr Uncertain significance ★★ ⚠ same type
ANK3 p.Ala1534Val Uncertain significance ★★ same type
ANK3 p.Ala1630Val Uncertain significance ★★ ⚠ same type
ANK3 p.Ala169Thr Uncertain significance ★★ same type
ANK3 p.Ala2023Thr Uncertain significance ★★ ⚠ same type
ANK3 p.Ala218Thr Uncertain significance ★★ same type
ANK3 p.Ala2223Thr Uncertain significance ★★ ⚠ 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/ank3-p-leu3077 (accessed [today's date]).

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