Is ALKBH3 p.Ala30Ser (c.88G>T) pathogenic?

ALKBH3 p.Ala30Ser (c.88G>T) is classified Uncertain significance in ALKBH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.0772); Ultra-rare (popmax 0.0242%, sas).

How common is ALKBH3 p.Ala30Ser (c.88G>T) in the general population?

ALKBH3 p.Ala30Ser (c.88G>T) is ultra-rare (popmax 0.0242%, sas) (gnomAD).

What do computational predictors say about ALKBH3 p.Ala30Ser (c.88G>T)?

AlphaMissense predicts likely benign (score 0.0772) — an in-silico prediction, not a clinical call.

ALKBH3 p.Ala30Ser

c.88G>T · VCV4273663

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0772 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0772	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -5.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.79	GERP -0.41
Regional constraint	o/e 1.03	unconstrained · MANE · 37 kb · p 0.63 · regional, not allelic
Overall
CADD	12.23	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 0.0242% South Asian · 22/91,004 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00136% 22/1,613,750 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: ALKBH3
Protein: p.Ala30Ser
Coding: c.88G>T
MANE Select: NM_139178
Type: single nucleotide variant
Location: chr11:43883093 (GRCh38)
Gene constraint: LOEUF 1.434 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.20 · 4 PDB
Residue 30: the 'disordered' region

Full ALKBH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALKBH3 p.Ala134Ser Uncertain significance ★ ⚠ same type
ALKBH3 p.Ala13Ser Uncertain significance ★ ⚠ same type
ALKBH3 p.Ala15Thr Uncertain significance ★ ⚠ same type
ALKBH3 p.Arg159His Uncertain significance ★ ⚠ same type
ALKBH3 p.Arg182His Uncertain significance ★ ⚠ same type
ALKBH3 p.Arg182Leu Uncertain significance ★ ⚠ same type
ALKBH3 p.Arg234Gly Uncertain significance ★ ⚠ same type
ALKBH3 p.Arg6Gln Uncertain significance ★ ⚠ same type

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/alkbh3-p-ala30ser (accessed [today's date]).

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