Is ALG5 p.Ser252Cys (c.755C>G) pathogenic?

ALG5 p.Ser252Cys (c.755C>G) is classified Uncertain significance in ALG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely benign (0.0747); Absent from gnomAD v4.1.

How common is ALG5 p.Ser252Cys (c.755C>G) in the general population?

ALG5 p.Ser252Cys (c.755C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG5 p.Ser252Cys (c.755C>G)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

ALG5 p.Ser252Cys

c.755C>G · rs2501484721 · VCV3111273

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0747 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0747	likely benign
REVEL	0.252	benign-leaning
SaProt	LLR -6.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.5	GERP 2.3, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 49 kb · p 9.9e-06 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALG5
Protein: p.Ser252Cys
Coding: c.755C>G
MANE Select: NM_013338
dbSNP: rs2501484721
Type: single nucleotide variant
Location: chr13:36965593 (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-ser252cys (accessed [today's date]).

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