Is ALG10B p.Ser442Arg (c.1324A>C) pathogenic?

ALG10B p.Ser442Arg (c.1324A>C) is classified Uncertain significance in ALG10B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-16). AlphaMissense: likely pathogenic (0.8574); Absent from gnomAD v4.1.

How common is ALG10B p.Ser442Arg (c.1324A>C) in the general population?

ALG10B p.Ser442Arg (c.1324A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG10B p.Ser442Arg (c.1324A>C)?

AlphaMissense predicts likely pathogenic (score 0.8574) — an in-silico prediction, not a clinical call.

ALG10B p.Ser442Arg

c.1324A>C · VCV4270193

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8574 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8574	likely pathogenic
REVEL	0.07	moderately benign-leaning
SaProt	LLR -11.17	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.79	phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 4,316 bp · p 0.37 · regional, not allelic
Overall
CADD	12.54	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

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: ALG10B
Protein: p.Ser442Arg
Coding: c.1324A>C
MANE Select: NM_001013620
Type: single nucleotide variant
Location: chr12:38321115 (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.Gln469= Benign ★★ same type
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

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-ser442arg (accessed [today's date]).

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