Is ALKBH1 p.Val69Leu (c.205G>T) pathogenic?

ALKBH1 p.Val69Leu (c.205G>T) is classified Uncertain significance in ALKBH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: likely benign (0.1112); Absent from gnomAD v4.1.

How common is ALKBH1 p.Val69Leu (c.205G>T) in the general population?

ALKBH1 p.Val69Leu (c.205G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALKBH1 p.Val69Leu (c.205G>T)?

AlphaMissense predicts likely benign (score 0.1112) — an in-silico prediction, not a clinical call.

ALKBH1 p.Val69Leu

c.205G>T · rs1487439731 · VCV2622286

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1112 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1112	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -3.62	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 0.68	GERP -0.21, phastCons 0.11
Regional constraint	o/e 0.99	unconstrained · MANE · 34 kb · p 0.74 · regional, not allelic
Overall
CADD	6.732	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

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: ALKBH1
Protein: p.Val69Leu
Coding: c.205G>T
MANE Select: NM_006020
dbSNP: rs1487439731
Type: single nucleotide variant
Location: chr14:77704456 (GRCh38)
Gene constraint: LOEUF 1.128 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.47 · 3 PDB
Residue 69: an α-helix

Full ALKBH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALKBH1 p.Ala348Gly Uncertain significance ★ ⚠ same type
ALKBH1 p.Ala48Val Uncertain significance ★ ⚠ same type
ALKBH1 p.Arg159Trp Uncertain significance ★ ⚠ same type
ALKBH1 p.Arg162Gln Uncertain significance ★ ⚠ same type
ALKBH1 p.Arg169His Uncertain significance ★ ⚠ same type
ALKBH1 p.Arg283Cys Uncertain significance ★ ⚠ same type
ALKBH1 p.Arg28His Uncertain significance ★ ⚠ same type
ALKBH1 p.Arg291Leu 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/alkbh1-p-val69leu (accessed [today's date]).

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