Is ANKRD17 p.Leu716Arg (c.2147T>G) pathogenic?

ANKRD17 p.Leu716Arg (c.2147T>G) is classified Likely pathogenic in ANKRD17 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-01). AlphaMissense: likely pathogenic (0.9993); Absent from gnomAD v4.1; Associated with Chopra-Amiel-Gordon syndrome.

What condition is associated with ANKRD17 p.Leu716Arg (c.2147T>G)?

ANKRD17 p.Leu716Arg (c.2147T>G) is associated with Chopra-Amiel-Gordon syndrome (ClinVar).

How common is ANKRD17 p.Leu716Arg (c.2147T>G) in the general population?

ANKRD17 p.Leu716Arg (c.2147T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD17 p.Leu716Arg (c.2147T>G)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

ANKRD17 p.Leu716Arg

c.2147T>G · rs2148821952 · VCV1342985

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Chopra-Amiel-Gordon syndrome

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic ✓ concordant with ClinVar · top 5% in ANKRD17
REVEL	0.969	strongly pathogenic-leaning
SaProt	LLR -14.57	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 7,354 bp · p 1.3e-08 · regional, not allelic
Overall
CADD	29.8	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

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.Leu716Arg
Coding: c.2147T>G
MANE Select: NM_032217
dbSNP: rs2148821952
Type: single nucleotide variant
Location: chr4:73142324 (GRCh38)
Gene constraint: LOEUF 0.118 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.73
Residue 716: 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-leu716arg (accessed [today's date]).

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