Is ALG10B p.Gln469= (c.1407A>G) pathogenic?

ALG10B p.Gln469= (c.1407A>G) is classified Benign in ALG10B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2015-03-03). Common (popmax 45.3%, nfe) — too common for a highly-penetrant pathogenic allele.

ALG10B p.Gln469=

Q: How common is ALG10B p.Gln469= (c.1407A>G) in the general population?

ALG10B p.Gln469= (c.1407A>G) is common (popmax 45.3%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1407A>G · rs35518352 · VCV1246184

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 45.3%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.75	phastCons 0.99
Overall
CADD	0.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 45.3% European (non-Finnish) · 532,953/1,177,360 alleles

Filtering AF 45.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 45.1%

Overall 41% 660,578/1,609,568 alleles · common exomes 608,394/1,457,572 · genomes 52,184/151,996 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	50%	2
Ashkenazi Jewishnot grpmax-eligible	45.7%	2
European (non-Finnish)grpmax	45.3%	2
Middle Eastern	42.4%	2
Finnishnot grpmax-eligible	39.6%	3
Remaining individualsnot grpmax-eligible	39.2%	3
South Asian	30.3%	3
Admixed American	24.7%	4
African / African-American	16.7%	6
East Asian	15.3%	7

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ALG10B
Protein: p.Gln469=
Coding: c.1407A>G
MANE Select: NM_001013620
dbSNP: rs35518352
Type: single nucleotide variant
Location: chr12:38321198 (GRCh38)
Gene constraint: LOEUF 1.018 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.14

Full ALG10B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALG10B p.Ala125Asp Uncertain significance ★ ⚠ same type
ALG10B p.Ala163Val Uncertain significance ★ ⚠ same type
ALG10B p.Ala176Gly Uncertain significance ★ ⚠ same type
ALG10B p.Ala2Ser Uncertain significance ★ ⚠ same type
ALG10B p.Ala2Val Uncertain significance ★ ⚠ same type
ALG10B p.Ala385Val Uncertain significance ★ ⚠ same type
ALG10B p.Arg186Trp Uncertain significance ★ ⚠ same type
ALG10B p.Arg279Gln 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/alg10b-p-gln469 (accessed [today's date]).

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