Is ANKRD17 p.Pro2240Arg (c.6719C>G) pathogenic?

ANKRD17 p.Pro2240Arg (c.6719C>G) is classified Likely pathogenic in ANKRD17 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-08). AlphaMissense: likely benign (0.2162); Very rare (popmax 0.000169%, nfe); Associated with Chopra-Amiel-Gordon syndrome.

What condition is associated with ANKRD17 p.Pro2240Arg (c.6719C>G)?

ANKRD17 p.Pro2240Arg (c.6719C>G) is associated with Chopra-Amiel-Gordon syndrome (ClinVar).

How common is ANKRD17 p.Pro2240Arg (c.6719C>G) in the general population?

ANKRD17 p.Pro2240Arg (c.6719C>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about ANKRD17 p.Pro2240Arg (c.6719C>G)?

AlphaMissense predicts likely benign (score 0.2162) — an in-silico prediction, not a clinical call.

ANKRD17 p.Pro2240Arg

c.6719C>G · rs1722731535 · VCV2442129

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2162 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Chopra-Amiel-Gordon syndrome

Computational evidence

Protein change
AlphaMissense	0.2162	likely benign ⚠ discordant with ClinVar
REVEL	0.074	moderately benign-leaning
SaProt	LLR -8.75	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 10	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 6,354 bp · p 0.16 · regional, not allelic
Overall
CADD	23.7	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 0.000169% European (non-Finnish) · 2/1,180,048 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,892 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.Pro2240Arg
Coding: c.6719C>G
MANE Select: NM_032217
dbSNP: rs1722731535
Type: single nucleotide variant
Location: chr4:73090909 (GRCh38)
Gene constraint: LOEUF 0.118 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.73
Residue 2240: a UniProt-annotated variant site (in cags)

Full ANKRD17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Chopra-Amiel-Gordon syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANKRD17 p.Arg1712His Uncertain significance ★★ ⚠ same condition
ANKRD17 p.Asn1251Ser Uncertain significance ★★ ⚠ same condition
ANKRD17 p.Asn2416Ser Uncertain significance ★★ ⚠ same condition
ANKRD17 p.Thr1577Ile Uncertain significance ★★ ⚠ same condition
ANKRD17 p.Thr2577Pro Uncertain significance ★★ ⚠ same condition
ANKRD17 p.Arg1112Ter Likely pathogenic ★ same condition
ANKRD17 p.Arg2434Gly Likely pathogenic ★ ⚠ same condition
ANKRD17 p.Arg2502Ter Pathogenic ★ 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-pro2240arg (accessed [today's date]).

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