Is ANKH p.Ile166= (c.498C>T) pathogenic?

ANKH p.Ile166= (c.498C>T) is classified Likely benign in ANKH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-11). Absent from gnomAD v4.1.

How common is ANKH p.Ile166= (c.498C>T) in the general population?

ANKH p.Ile166= (c.498C>T) is absent from gnomAD v4.1 (gnomAD).

ANKH p.Ile166=

c.498C>T · rs1242701419 · VCV1967875

Likely benign Single submitter

Classification

Likely benign

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 carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.65, phastCons 1
Overall
CADD	12.47	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.Ile166=
Coding: c.498C>T
MANE Select: NM_054027
dbSNP: rs1242701419
Type: single nucleotide variant
Location: chr5:14755879 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.57

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

Similar variants

ANKH p.Ile166Thr 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
ANKH p.Arg453Gln 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-ile166 (accessed [today's date]).

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