Is ALG10B p.Ser465fs (c.1395_1398del) pathogenic?

ALG10B p.Ser465fs (c.13951398del) is classified Benign in ALG10B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). Rare (popmax 0.139%, afr).

How common is ALG10B p.Ser465fs (c.1395_1398del) in the general population?

ALG10B p.Ser465fs (c.1395_1398del) is rare (popmax 0.139%, afr) (gnomAD).

ALG10B p.Ser465fs

c.1395_1398del · VCV3778123

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.139%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.139% African / African-American · 104/74,974 alleles

Filtering AF 0.117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.109%

Overall 0.0143% 231/1,612,342 alleles · rare exomes 155/1,460,088 · genomes 76/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.139%	721
East Asian	0.0692%	1,446
Admixed American	0.0334%	2,992
Remaining individualsnot grpmax-eligible	0.024%	4,162
South Asian	0.00552%	18,118
European (non-Finnish)	0.00466%	21,442
Finnishnot grpmax-eligible	0.00156%	63,954

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.Ser465fs
Coding: c.1395_1398del
MANE Select: NM_001013620
Type: Deletion
Location: chr12:38321184 (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

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-ser465fs (accessed [today's date]).

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