Is ANKH p.Glu492= (c.1476A>G) pathogenic?

ANKH p.Glu492= (c.1476A>G) is classified Uncertain significance in ANKH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-23). Absent from gnomAD v4.1.

How common is ANKH p.Glu492= (c.1476A>G) in the general population?

ANKH p.Glu492= (c.1476A>G) is absent from gnomAD v4.1 (gnomAD).

ANKH p.Glu492=

c.1476A>G · rs751331156 · VCV1911459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.70	donor gain · deltas
Pangolin	Δ0.77	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -4.3	GERP -2.9
Overall
CADD	16.83	PHRED · no single calibrated threshold — expert panels disagree

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: ANKH
Protein: p.Glu492=
Coding: c.1476A>G
MANE Select: NM_054027
dbSNP: rs751331156
Type: single nucleotide variant
Location: chr5:14711200 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.57
Residue 492: the 'disordered' region

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

Similar variants

ANKH p.Glu492Lys Uncertain significance ★★ ⚠ same residue
ANKH p.Glu492Val Uncertain significance ★ same residue
ANKH c.1142-4A>G Pathogenic/Likely pathogenic ★★ same type
ANKH c.96+5G>A Uncertain significance ★★ same type
ANKH c.*3752G>A Uncertain significance ★★ same type
ANKH p.Ala136Thr Uncertain significance ★★ ⚠ same type
ANKH p.Ala201Thr Uncertain significance ★★ ⚠ same type
ANKH p.Ala448Thr Uncertain significance ★★ ⚠ same type

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/ankh-p-glu492 (accessed [today's date]).

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