Is ANKRD17 p.Ser2282Cys (c.6845C>G) pathogenic?

ANKRD17 p.Ser2282Cys (c.6845C>G) is classified Uncertain significance in ANKRD17 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). AlphaMissense: likely benign (0.1001); Very rare (popmax 0.0011%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ANKRD17 p.Ser2282Cys (c.6845C>G)?

ANKRD17 p.Ser2282Cys (c.6845C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ANKRD17 p.Ser2282Cys (c.6845C>G) in the general population?

ANKRD17 p.Ser2282Cys (c.6845C>G) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about ANKRD17 p.Ser2282Cys (c.6845C>G)?

AlphaMissense predicts likely benign (score 0.1001) — an in-silico prediction, not a clinical call.

ANKRD17 p.Ser2282Cys

c.6845C>G · rs146464946 · VCV2463767

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1001 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1001	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -9.21	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 6,354 bp · p 0.16 · regional, not allelic
Overall
CADD	27.1	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 0.0011% European (non-Finnish) · 13/1,180,048 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00124% 20/1,614,068 alleles · very rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.768%	130
European (non-Finnish)grpmax	0.0011%	90,773

Amish 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.Ser2282Cys
Coding: c.6845C>G
MANE Select: NM_032217
dbSNP: rs146464946
Type: single nucleotide variant
Location: chr4:73090783 (GRCh38)
Gene constraint: LOEUF 0.118 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.73
Residue 2282: 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-ser2282cys (accessed [today's date]).

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