Is ALG10B p.Ser20Pro (c.58T>C) pathogenic?

ALG10B p.Ser20Pro (c.58T>C) is classified Uncertain significance in ALG10B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely pathogenic (0.8211); Very rare (popmax 0.000932%, nfe).

How common is ALG10B p.Ser20Pro (c.58T>C) in the general population?

ALG10B p.Ser20Pro (c.58T>C) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about ALG10B p.Ser20Pro (c.58T>C)?

AlphaMissense predicts likely pathogenic (score 0.8211) — an in-silico prediction, not a clinical call.

ALG10B p.Ser20Pro

c.58T>C · VCV4639952

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8211 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8211	likely pathogenic
REVEL	0.265	benign-leaning
SaProt	LLR -15.22	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 7.4	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 4,316 bp · p 0.37 · regional, not allelic
Overall
CADD	25.4	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 0.000932% European (non-Finnish) · 11/1,180,022 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000681% 11/1,614,146 alleles · very rare exomes 11/1,461,894 · genomes 0/152,252 · joint denominator

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.Ser20Pro
Coding: c.58T>C
MANE Select: NM_001013620
Type: single nucleotide variant
Location: chr12:38316951 (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-ser20pro (accessed [today's date]).

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