Is ANKH p.Met48Val (c.142A>G) pathogenic?

ANKH p.Met48Val (c.142A>G) is classified Uncertain significance in ANKH (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-13). AlphaMissense: likely benign (0.338); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ANKH p.Met48Val (c.142A>G)?

ANKH p.Met48Val (c.142A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ANKH p.Met48Val (c.142A>G) in the general population?

ANKH p.Met48Val (c.142A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKH p.Met48Val (c.142A>G)?

AlphaMissense predicts likely benign (score 0.338) — an in-silico prediction, not a clinical call.

ANKH p.Met48Val

c.142A>G · VCV4858507

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.338 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.338	likely benign
REVEL	0.751	pathogenic-leaning
SaProt	LLR -4.70	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 160 kb · p 1.1e-21 · regional, not allelic
Overall
CADD	23.1	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

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.Met48Val
Coding: c.142A>G
MANE Select: NM_054027
Type: single nucleotide variant
Location: chr5:14769146 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.57
Residue 48: a UniProt-annotated variant site (in ccal2)

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.Met48Lys Uncertain significance ★ ⚠ same residue
ANKH p.Met48Thr Pathogenic ⚠ same residue
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

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-met48val (accessed [today's date]).

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