Is ANKRD17 p.Ala474Ser (c.1420G>T) pathogenic?

ANKRD17 p.Ala474Ser (c.1420G>T) is classified Uncertain significance in ANKRD17 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-11). AlphaMissense: likely pathogenic (0.7875); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ANKRD17 p.Ala474Ser (c.1420G>T)?

ANKRD17 p.Ala474Ser (c.1420G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANKRD17 p.Ala474Ser (c.1420G>T) in the general population?

ANKRD17 p.Ala474Ser (c.1420G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD17 p.Ala474Ser (c.1420G>T)?

AlphaMissense predicts likely pathogenic (score 0.7875) — an in-silico prediction, not a clinical call.

ANKRD17 p.Ala474Ser

c.1420G>T · VCV4841098

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7875 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7875	likely pathogenic
REVEL	0.778	moderately pathogenic-leaning
SaProt	LLR -10.93	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 4,100 bp · p 6.7e-17 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Ala474Ser
Coding: c.1420G>T
MANE Select: NM_032217
Type: single nucleotide variant
Location: chr4:73148960 (GRCh38)
Gene constraint: LOEUF 0.118 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.73

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-ala474ser (accessed [today's date]).

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