Is ALG8 p.Arg215Gln (c.644G>A) pathogenic?

ALG8 p.Arg215Gln (c.644G>A) is classified Uncertain significance in ALG8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-21). AlphaMissense: likely benign (0.172); Very rare (popmax 0.00667%, amr); Associated with Inborn genetic diseases.

What condition is associated with ALG8 p.Arg215Gln (c.644G>A)?

ALG8 p.Arg215Gln (c.644G>A) is associated with Inborn genetic diseases, ALG8-congenital disorder of glycosylation (ClinVar).

How common is ALG8 p.Arg215Gln (c.644G>A) in the general population?

ALG8 p.Arg215Gln (c.644G>A) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about ALG8 p.Arg215Gln (c.644G>A)?

AlphaMissense predicts likely benign (score 0.172) — an in-silico prediction, not a clinical call.

ALG8 p.Arg215Gln

c.644G>A · rs201602294 · VCV2142991

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.172 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.172	likely benign
REVEL	0.689	pathogenic-leaning
SaProt	LLR -10.93	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.28	donor loss, 29 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.14 · regional, not allelic
Overall
CADD	29.6	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 0.00667% Admixed American · 4/59,968 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000682% 11/1,613,910 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,992
East Asian	0.00223%	44,880
African / African-American	0.00134%	74,894
European (non-Finnish)	0.000424%	236,004

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.Arg215Gln
Coding: c.644G>A
MANE Select: NM_024079
dbSNP: rs201602294
Type: single nucleotide variant
Location: chr11:78114295 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 215: a UniProt-annotated variant site (in pcld3)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG8-congenital disorder of glycosylation

Similar variants

ALG8 p.Arg215Ter Likely pathogenic ★ same residue
ALG8 p.Arg215Pro Uncertain significance ★ ⚠ same residue
ALG8 p.Arg215= Likely benign ★ same residue
ALG8 c.368+2T>G Likely pathogenic ★★ same condition
ALG8 c.674-2A>G Likely pathogenic ★★ same condition
ALG8 c.777+1G>A Likely pathogenic ★★ same condition
ALG8 c.95+1G>A Likely pathogenic ★★ same condition
ALG8 p.Arg179Ter Pathogenic/Likely pathogenic ★★ same condition

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-arg215gln (accessed [today's date]).

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