Is ANKH p.Val485Met (c.1453G>A) pathogenic?

ANKH p.Val485Met (c.1453G>A) is classified Benign/Likely benign in ANKH (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-18). AlphaMissense: likely benign (0.1249); Rare (popmax 0.902%, afr); Associated with chondrocalcinosis 2.

What condition is associated with ANKH p.Val485Met (c.1453G>A)?

ANKH p.Val485Met (c.1453G>A) is associated with chondrocalcinosis 2, craniometaphyseal dysplasia, autosomal dominant (ClinVar).

How common is ANKH p.Val485Met (c.1453G>A) in the general population?

ANKH p.Val485Met (c.1453G>A) is rare (popmax 0.902%, afr) (gnomAD).

How is Familial calcium pyrophosphate deposition inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ANKH p.Val485Met (c.1453G>A)?

AlphaMissense predicts likely benign (score 0.1249) — an in-silico prediction, not a clinical call.

ANKH p.Val485Met

c.1453G>A · rs143550972 · VCV351498

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1249 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.902%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

chondrocalcinosis 2

Computational evidence

Protein change
AlphaMissense	0.1249	likely benign
REVEL	0.311	indeterminate
SaProt	LLR -8.04	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.39	unconstrained · MANE · 80 bp · p 0.018 · regional, not allelic
Overall
CADD	27.0	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 0.902% African / African-American · 677/75,044 alleles

Filtering AF 0.846% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.823%

Overall 0.0499% 806/1,614,152 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.902%	111
Remaining individualsnot grpmax-eligible	0.088%	1,137
Admixed American	0.0866%	1,154
Middle Eastern	0.0165%	6,062
South Asian	0.0022%	45,541
European (non-Finnish)	0.00161%	62,106

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
Protein: p.Val485Met
Coding: c.1453G>A
MANE Select: NM_054027
dbSNP: rs143550972
Type: single nucleotide variant
Location: chr5:14711223 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.57
Residue 485: the 'disordered' region

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

Disease context

chondrocalcinosis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: craniometaphyseal dysplasia, autosomal dominant

For Familial calcium pyrophosphate deposition (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult

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-p-val485met (accessed [today's date]).

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