Is ANKH p.Arg372Gln (c.1115G>A) pathogenic?

ANKH p.Arg372Gln (c.1115G>A) is classified Conflicting classifications of pathogenicity in ANKH (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-21). AlphaMissense: likely benign (0.0702); Ultra-rare (popmax 0.025%, amr); Associated with Inborn genetic diseases.

What condition is associated with ANKH p.Arg372Gln (c.1115G>A)?

ANKH p.Arg372Gln (c.1115G>A) is associated with Inborn genetic diseases, chondrocalcinosis 2, craniometaphyseal dysplasia, autosomal dominant (ClinVar).

How common is ANKH p.Arg372Gln (c.1115G>A) in the general population?

ANKH p.Arg372Gln (c.1115G>A) is ultra-rare (popmax 0.025%, amr) (gnomAD).

What do computational predictors say about ANKH p.Arg372Gln (c.1115G>A)?

AlphaMissense predicts likely benign (score 0.0702) — an in-silico prediction, not a clinical call.

ANKH p.Arg372Gln

c.1115G>A · rs544848340 · VCV351504

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0702 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0702	likely benign
REVEL	0.488	indeterminate
SaProt	LLR -8.53	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 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 160 kb · p 1.1e-21 · regional, not allelic
Overall
CADD	26.7	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 0.025% Admixed American · 15/59,988 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.00793% 128/1,613,860 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	3,999
Middle Eastern	0.0164%	6,084
European (non-Finnish)	0.00864%	11,568
Remaining individualsnot grpmax-eligible	0.0064%	15,617
Finnishnot grpmax-eligible	0.00625%	15,999
African / African-American	0.00134%	74,892
South Asian	0.0011%	91,078

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.Arg372Gln
Coding: c.1115G>A
MANE Select: NM_054027
dbSNP: rs544848340
Type: single nucleotide variant
Location: chr5:14716732 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: chondrocalcinosis 2 craniometaphyseal dysplasia, autosomal dominant

Similar variants

ANKH p.Arg372Trp Uncertain significance ★ ⚠ same residue
ANKH p.Arg372= Likely benign ★ same residue
ANKH c.1142-4A>G Pathogenic/Likely pathogenic ★★ same condition
ANKH c.*3752G>A Uncertain significance ★★ same condition
ANKH p.Ala136Thr Uncertain significance ★★ ⚠ same condition
ANKH p.Arg453Gln Uncertain significance ★★ ⚠ same condition
ANKH p.Asn306Asp Uncertain significance ★★ ⚠ same condition
ANKH p.Asn347Ser Uncertain significance ★★ ⚠ 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-arg372gln (accessed [today's date]).

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