Is ANKH p.Glu480Val (c.1439A>T) pathogenic?

ANKH p.Glu480Val (c.1439A>T) is classified Uncertain significance in ANKH (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.1216); Ultra-rare (popmax 0.0646%, eas); Associated with Inborn genetic diseases.

What condition is associated with ANKH p.Glu480Val (c.1439A>T)?

ANKH p.Glu480Val (c.1439A>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANKH p.Glu480Val (c.1439A>T) in the general population?

ANKH p.Glu480Val (c.1439A>T) is ultra-rare (popmax 0.0646%, eas) (gnomAD).

What do computational predictors say about ANKH p.Glu480Val (c.1439A>T)?

AlphaMissense predicts likely benign (score 0.1216) — an in-silico prediction, not a clinical call.

ANKH p.Glu480Val

c.1439A>T · rs777112283 · VCV501584

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1216 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0646%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1216	likely benign
REVEL	0.37	indeterminate
SaProt	LLR -6.08	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 7.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.39	unconstrained · MANE · 80 bp · p 0.018 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0646% East Asian · 29/44,872 alleles

Filtering AF 0.0461% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.04%

Overall 0.00242% 39/1,613,974 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0646%	1,547
Admixed American	0.005%	20,001
European (non-Finnish)	0.000593%	168,573

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.Glu480Val
Coding: c.1439A>T
MANE Select: NM_054027
dbSNP: rs777112283
Type: single nucleotide variant
Location: chr5:14711237 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.57
Residue 480: the 'disordered' region

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

Similar variants

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
ANKH p.Asp218Asn Uncertain significance ★★ ⚠ same condition
ANKH p.Glu47Lys Uncertain significance ★★ ⚠ same condition
ANKH p.Glu486Lys Uncertain significance ★★ ⚠ same condition
ANKH p.Glu492Lys 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-glu480val (accessed [today's date]).

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