Is ALG5 p.Lys93Glu (c.277A>G) pathogenic?

ALG5 p.Lys93Glu (c.277A>G) is classified Likely benign in ALG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely benign (0.0499); Rare (popmax 0.149%, mid).

How common is ALG5 p.Lys93Glu (c.277A>G) in the general population?

ALG5 p.Lys93Glu (c.277A>G) is rare (popmax 0.149%, mid) (gnomAD).

What do computational predictors say about ALG5 p.Lys93Glu (c.277A>G)?

AlphaMissense predicts likely benign (score 0.0499) — an in-silico prediction, not a clinical call.

ALG5 p.Lys93Glu

c.277A>G · VCV3852276

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0499 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.149%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0499	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -3.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.53 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.9	GERP -1.3, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 49 kb · p 9.9e-06 · regional, not allelic
Overall
CADD	16.37	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 0.149% Middle Eastern · 9/6,052 alleles

Filtering AF 0.0775% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0579%

Overall 0.00372% 60/1,612,848 alleles · rare exomes 57/1,460,702 · genomes 3/152,146 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.149%	672
African / African-American	0.0174%	5,758
Remaining individualsnot grpmax-eligible	0.0128%	7,803
South Asian	0.0033%	30,303
European (non-Finnish)	0.0022%	45,358
Admixed American	0.00167%	59,882

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: ALG5
Protein: p.Lys93Glu
Coding: c.277A>G
MANE Select: NM_013338
Type: single nucleotide variant
Location: chr13:36994997 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 92.29

Full ALG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALG5 p.Thr249Met Uncertain significance ★★ ⚠ same type
ALG5 c.239-2A>G Likely pathogenic ★ same type
ALG5 p.Arg39Ter Likely pathogenic ★ same type
ALG5 p.Arg97Ter Pathogenic ★ same type
ALG5 p.Trp224Ter Likely pathogenic ★ same type
ALG5 p.Ala14Thr Uncertain significance ★ ⚠ same type
ALG5 p.Ala16Ser Uncertain significance ★ ⚠ same type
ALG5 p.Ala17Val 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/alg5-p-lys93glu (accessed [today's date]).

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