Is ATP6V1B1 p.Met26Val (c.76A>G) pathogenic?

ATP6V1B1 p.Met26Val (c.76A>G) is classified Conflicting classifications of pathogenicity in ATP6V1B1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-08-19). AlphaMissense: likely benign (0.0663); Very rare (popmax 0.00203%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ATP6V1B1 p.Met26Val (c.76A>G)?

ATP6V1B1 p.Met26Val (c.76A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ATP6V1B1 p.Met26Val (c.76A>G) in the general population?

ATP6V1B1 p.Met26Val (c.76A>G) is very rare (popmax 0.00203%, nfe) (gnomAD).

What do computational predictors say about ATP6V1B1 p.Met26Val (c.76A>G)?

AlphaMissense predicts likely benign (score 0.0663) — an in-silico prediction, not a clinical call.

ATP6V1B1 p.Met26Val

c.76A>G · rs781815747 · VCV2074560

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0663 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0663	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -4.55	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 -3.1	GERP -2.9
Regional constraint	o/e 0.93	unconstrained · MANE · 29 kb · p 0.078 · regional, not allelic
Overall
CADD	0.008	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 0.00203% European (non-Finnish) · 24/1,179,924 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00149% 24/1,613,824 alleles · very 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: ATP6V1B1
Protein: p.Met26Val
Coding: c.76A>G
MANE Select: NM_001692
dbSNP: rs781815747
Type: single nucleotide variant
Location: chr2:70936030 (GRCh38)
Gene constraint: LOEUF 0.827 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.21

Full ATP6V1B1 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

ATP6V1B1 p.Met26Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
ATP6V1B1 p.Arg114Ter Pathogenic ★★ same condition
ATP6V1B1 p.Gly78Arg Pathogenic/Likely pathogenic ★★ same condition
ATP6V1B1 p.Ala141Val Uncertain significance ★★ ⚠ same condition
ATP6V1B1 p.Ala28Val Uncertain significance ★★ ⚠ same condition
ATP6V1B1 p.Ala2Ser Uncertain significance ★★ ⚠ same condition
ATP6V1B1 p.Arg102Lys Uncertain significance ★★ ⚠ same condition
ATP6V1B1 p.Arg114Gln 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/atp6v1b1-p-met26val (accessed [today's date]).

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