Is ANKH c.*4635A>C pathogenic?

ANKH c.4635A>C is classified Uncertain significance in ANKH (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0103%, nfe); Associated with craniometaphyseal dysplasia, autosomal dominant.

How common is ANKH c.*4635A>C in the general population?

ANKH c.*4635A>C is ultra-rare (popmax 0.0103%, nfe) (gnomAD).

ANKH c.*4635A>C

Q: What condition is associated with ANKH c.*4635A>C?

ANKH c.*4635A>C is associated with craniometaphyseal dysplasia, autosomal dominant, chondrocalcinosis 2 (ClinVar).

rs1036873430 · VCV907853

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, nfe)

Conditions

craniometaphyseal dysplasia, autosomal dominant

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 0.36	GERP -2.4, phastCons 0.003
Non-coding constraint	Z 1.44	1 kb window · o/e 0.90 · regional · uncalibrated
Overall
CADD	1.845	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0103% European (non-Finnish) · 7/68,038 alleles

Filtering AF 0.00476% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00334%

Overall 0.0046% 7/152,234 alleles · ultra-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: ANKH
Coding: c.*4635A>C
MANE Select: NM_054027
dbSNP: rs1036873430
Type: single nucleotide variant
Location: chr5:14706562 (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

Disease context

craniometaphyseal dysplasia, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: chondrocalcinosis 2

Similar variants

ANKH c.1142-4A>G Pathogenic/Likely pathogenic ★★ same condition
ANKH c.*3752G>A Uncertain significance ★★ same condition
ANKH p.Val313Met Uncertain significance ★★ ⚠ same condition
ANKH c.1011+15T>G Benign ★★ same condition
ANKH c.1012-11T>G Benign/Likely benign ★★ same condition
ANKH c.1265+6T>C Benign ★★ same condition
ANKH c.1266-6C>T Benign/Likely benign ★★ same condition
ANKH c.1365+13C>T Benign ★★ 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/ankh-c-star-4635a-c (accessed [today's date]).

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