Is ALG11 p.Ser419= (c.1257G>A) pathogenic?

ALG11 p.Ser419= (c.1257G>A) is classified Likely benign in ALG11 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-03-11). Very rare (popmax 0.005%, amr).

How common is ALG11 p.Ser419= (c.1257G>A) in the general population?

ALG11 p.Ser419= (c.1257G>A) is very rare (popmax 0.005%, amr) (gnomAD).

ALG11 p.Ser419=

c.1257G>A · rs770888492 · VCV383290

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.122	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.3	GERP -3.4
Overall
CADD	1.973	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,980 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00112% 18/1,613,916 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,993
Remaining individualsnot grpmax-eligible	0.0048%	20,827
East Asian	0.00223%	44,888
South Asian	0.0011%	91,086
European (non-Finnish)	0.000847%	118,002

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: ALG11
Protein: p.Ser419=
Coding: c.1257G>A
MANE Select: NM_021645 · reported on NM_001004127
dbSNP: rs770888492
Type: single nucleotide variant
Location: chr13:52028368 (GRCh38)

Full ALG11 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/alg11-p-ser419 (accessed [today's date]).

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