Is ALG1 p.Leu233Val (c.697C>G) pathogenic?

ALG1 p.Leu233Val (c.697C>G) is classified Uncertain significance in ALG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-11). AlphaMissense: likely benign (0.2092); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ALG1 p.Leu233Val (c.697C>G)?

ALG1 p.Leu233Val (c.697C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ALG1 p.Leu233Val (c.697C>G) in the general population?

ALG1 p.Leu233Val (c.697C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG1 p.Leu233Val (c.697C>G)?

AlphaMissense predicts likely benign (score 0.2092) — an in-silico prediction, not a clinical call.

ALG1 p.Leu233Val

c.697C>G · rs2505860109 · VCV2610624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2092 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,603,526)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2092	likely benign
REVEL	0.527	indeterminate
SaProt	LLR -9.80	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	24.6	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

No allele count reported in gnomAD v4.1 (AN 1,603,526). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALG1
Protein: p.Leu233Val
Coding: c.697C>G
MANE Select: NM_019109
dbSNP: rs2505860109
Type: single nucleotide variant
Location: chr16:5077974 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24

Full ALG1 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

Similar variants

ALG1 p.Leu233= Likely benign ★ same residue
ALG1 p.Ala360Val Pathogenic/Likely pathogenic ★★ same condition
ALG1 p.Gln342Pro Pathogenic/Likely pathogenic ★★ ⚠ same condition
ALG1 p.Ala278Thr Uncertain significance ★★ ⚠ same condition
ALG1 p.Arg257Gln Uncertain significance ★★ ⚠ same condition
ALG1 p.Asn311Lys Uncertain significance ★★ ⚠ same condition
ALG1 p.Asn80His Uncertain significance ★★ ⚠ same condition
ALG1 p.Asp252Glu Uncertain significance ★★ ⚠ 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/alg1-p-leu233val (accessed [today's date]).

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