Is ALG8 p.Ser393Asn (c.1178G>A) pathogenic?

ALG8 p.Ser393Asn (c.1178G>A) is classified Uncertain significance in ALG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2013-06-12). AlphaMissense: likely pathogenic (0.7635); Very rare (popmax 0.00856%, nfe).

How common is ALG8 p.Ser393Asn (c.1178G>A) in the general population?

ALG8 p.Ser393Asn (c.1178G>A) is very rare (popmax 0.00856%, nfe) (gnomAD).

What do computational predictors say about ALG8 p.Ser393Asn (c.1178G>A)?

AlphaMissense predicts likely pathogenic (score 0.7635) — an in-silico prediction, not a clinical call.

ALG8 p.Ser393Asn

c.1178G>A · rs398124390 · VCV96089

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7635 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00856%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7635	likely pathogenic
REVEL	0.685	pathogenic-leaning
SaProt	LLR -11.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.42	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.27	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.14 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00856% European (non-Finnish) · 101/1,179,942 alleles

Filtering AF 0.00716% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00668%

Overall 0.00644% 104/1,613,812 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00856%	11,683
African / African-American	0.00267%	37,450
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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: ALG8
Protein: p.Ser393Asn
Coding: c.1178G>A
MANE Select: NM_024079
dbSNP: rs398124390
Type: single nucleotide variant
Location: chr11:78106807 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 393: a UniProt-annotated variant site (in pcld3)

Full ALG8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALG8 c.368+2T>G Likely pathogenic ★★ same type
ALG8 c.674-2A>G Likely pathogenic ★★ same type
ALG8 c.777+1G>A Likely pathogenic ★★ same type
ALG8 c.95+1G>A Likely pathogenic ★★ same type
ALG8 p.Arg179Ter Pathogenic/Likely pathogenic ★★ same type
ALG8 p.Arg229Ter Pathogenic/Likely pathogenic ★★ same type
ALG8 p.Arg268Ter Pathogenic/Likely pathogenic ★★ same type
ALG8 p.Arg364Ter Pathogenic/Likely pathogenic ★★ 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/alg8-p-ser393asn (accessed [today's date]).

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