Is ANKRD17 p.Ile2446= (c.7338T>A) pathogenic?

ANKRD17 p.Ile2446= (c.7338T>A) is classified Uncertain significance in ANKRD17 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). Very rare (popmax 0.000339%, nfe); Associated with ANKRD17-related disorder.

What condition is associated with ANKRD17 p.Ile2446= (c.7338T>A)?

ANKRD17 p.Ile2446= (c.7338T>A) is associated with ANKRD17-related disorder (ClinVar).

How common is ANKRD17 p.Ile2446= (c.7338T>A) in the general population?

ANKRD17 p.Ile2446= (c.7338T>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

ANKRD17 p.Ile2446=

c.7338T>A · rs374167645 · VCV2629916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

ANKRD17-related disorder

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 3.1	GERP 1.8, phastCons 1
Overall
CADD	9.447	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,028 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,076 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)grpmax	0.000339%	295,007

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ANKRD17
Protein: p.Ile2446=
Coding: c.7338T>A
MANE Select: NM_032217
dbSNP: rs374167645
Type: single nucleotide variant
Location: chr4:73078712 (GRCh38)
Gene constraint: LOEUF 0.118 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.73
Residue 2446: a UniProt-annotated variant site (in cags)

Full ANKRD17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ANKRD17-related disorder

Similar variants

ANKRD17 p.Gly587Glu Uncertain significance ★★ ⚠ same condition
ANKRD17 p.Ala437Asp Uncertain significance ★ ⚠ same condition
ANKRD17 p.Asp138His Uncertain significance ★ ⚠ same condition
ANKRD17 p.Asp2470Gly Uncertain significance ★ ⚠ same condition
ANKRD17 p.Gln931Lys Uncertain significance ★ ⚠ same condition
ANKRD17 p.Ile1346Thr Uncertain significance ★ ⚠ same condition
ANKRD17 p.Lys1942Asn Uncertain significance ★ ⚠ same condition
ANKRD17 p.Lys1942Gln 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/ankrd17-p-ile2446 (accessed [today's date]).

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