Is ALG5 p.Leu265Val (c.793C>G) pathogenic?

ALG5 p.Leu265Val (c.793C>G) is classified Uncertain significance in ALG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely pathogenic (0.5749); Very rare (popmax 0.00968%, amr).

How common is ALG5 p.Leu265Val (c.793C>G) in the general population?

ALG5 p.Leu265Val (c.793C>G) is very rare (popmax 0.00968%, amr) (gnomAD).

What do computational predictors say about ALG5 p.Leu265Val (c.793C>G)?

AlphaMissense predicts likely pathogenic (score 0.5749) — an in-silico prediction, not a clinical call.

ALG5 p.Leu265Val

c.793C>G · rs763549556 · VCV3111280

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5749 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00968%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5749	likely pathogenic
REVEL	0.26	benign-leaning
SaProt	LLR -12.42	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 49 kb · p 9.9e-06 · regional, not allelic
Overall
CADD	27.0	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 0.00968% Admixed American · 5/51,674 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00245%

Overall 0.000507% 8/1,579,370 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00968%	10,335
South Asian	0.00237%	42,213
Remaining individualsnot grpmax-eligible	0.00164%	61,124

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.Leu265Val
Coding: c.793C>G
MANE Select: NM_013338
dbSNP: rs763549556
Type: single nucleotide variant
Location: chr13:36952580 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 92.29
Residue 265: a UniProt-annotated variant site (in pkd7)

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-leu265val (accessed [today's date]).

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