Is ANKRD17 p.Ile1326Val (c.3976A>G) pathogenic?

ANKRD17 p.Ile1326Val (c.3976A>G) is classified Uncertain significance in ANKRD17 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-22). AlphaMissense: likely pathogenic (0.9456); Very rare (popmax 0.00144%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ANKRD17 p.Ile1326Val (c.3976A>G)?

ANKRD17 p.Ile1326Val (c.3976A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ANKRD17 p.Ile1326Val (c.3976A>G) in the general population?

ANKRD17 p.Ile1326Val (c.3976A>G) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about ANKRD17 p.Ile1326Val (c.3976A>G)?

AlphaMissense predicts likely pathogenic (score 0.9456) — an in-silico prediction, not a clinical call.

ANKRD17 p.Ile1326Val

c.3976A>G · rs749511206 · VCV2219441

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9456 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9456	likely pathogenic
REVEL	0.265	benign-leaning
SaProt	LLR -8.09	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 11 kb · p 1.8e-32 · regional, not allelic
Overall
CADD	24.3	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 0.00144% European (non-Finnish) · 17/1,180,018 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00105% 17/1,614,000 alleles · very rare

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.Ile1326Val
Coding: c.3976A>G
MANE Select: NM_032217
dbSNP: rs749511206
Type: single nucleotide variant
Location: chr4:73120211 (GRCh38)
Gene constraint: LOEUF 0.118 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.73
Residue 1326: a UniProt-annotated variant site (in cags)

Full ANKRD17 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

ANKRD17 p.Ile1326Thr Uncertain significance ★ ⚠ same residue
ANKRD17 p.Arg1712His Uncertain significance ★★ ⚠ same condition
ANKRD17 p.Arg418Gln Uncertain significance ★★ ⚠ same condition
ANKRD17 p.Arg52Cys Uncertain significance ★★ ⚠ same condition
ANKRD17 p.Cys1690Tyr Uncertain significance ★★ ⚠ same condition
ANKRD17 p.Gln907Pro Uncertain significance ★★ ⚠ same condition
ANKRD17 p.Glu1508Asp Uncertain significance ★★ ⚠ same condition
ANKRD17 p.Glu1526Ala 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-ile1326val (accessed [today's date]).

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