Is ANKRD17 p.Pro1888Ser (c.5662C>T) pathogenic?

ANKRD17 p.Pro1888Ser (c.5662C>T) is classified Uncertain significance in ANKRD17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely benign (0.1289); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with ANKRD17 p.Pro1888Ser (c.5662C>T)?

ANKRD17 p.Pro1888Ser (c.5662C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANKRD17 p.Pro1888Ser (c.5662C>T) in the general population?

ANKRD17 p.Pro1888Ser (c.5662C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ANKRD17 p.Pro1888Ser (c.5662C>T)?

AlphaMissense predicts likely benign (score 0.1289) — an in-silico prediction, not a clinical call.

ANKRD17 p.Pro1888Ser

c.5662C>T · VCV4101704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1289 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1289	likely benign
REVEL	0.553	indeterminate
SaProt	LLR -7.72	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 503 bp · p 3.7e-05 · regional, not allelic
Overall
CADD	28.6	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

Grpmax group 0.00133% African / African-American · 1/75,052 alleles

Overall 6.84e-05% 1/1,461,894 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.Pro1888Ser
Coding: c.5662C>T
MANE Select: NM_032217
Type: single nucleotide variant
Location: chr4:73091966 (GRCh38)
Gene constraint: LOEUF 0.118 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.73
Residue 1888: 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-pro1888ser (accessed [today's date]).

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