Is ANKRD17 p.Val2128Phe (c.6382G>T) pathogenic?

ANKRD17 p.Val2128Phe (c.6382G>T) is classified Uncertain significance in ANKRD17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-18). AlphaMissense: likely benign (0.1131); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ANKRD17 p.Val2128Phe (c.6382G>T)?

ANKRD17 p.Val2128Phe (c.6382G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANKRD17 p.Val2128Phe (c.6382G>T) in the general population?

ANKRD17 p.Val2128Phe (c.6382G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD17 p.Val2128Phe (c.6382G>T)?

AlphaMissense predicts likely benign (score 0.1131) — an in-silico prediction, not a clinical call.

ANKRD17 p.Val2128Phe

c.6382G>T · VCV4101754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1131 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1131	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.92, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 6,354 bp · p 0.16 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANKRD17
Protein: p.Val2128Phe
Coding: c.6382G>T
MANE Select: NM_032217
Type: single nucleotide variant
Location: chr4:73091246 (GRCh38)
Gene constraint: LOEUF 0.118 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.73
Residue 2128: the 'disordered' region; 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.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
ANKRD17 p.Ile2465Phe 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-val2128phe (accessed [today's date]).

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