Is ALG3 p.Leu264Phe (c.790C>T) pathogenic?

ALG3 p.Leu264Phe (c.790C>T) is classified Uncertain significance in ALG3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-08-09). AlphaMissense: likely benign (0.1133); Rare (popmax 0.111%, afr); Associated with Inborn genetic diseases.

What condition is associated with ALG3 p.Leu264Phe (c.790C>T)?

ALG3 p.Leu264Phe (c.790C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ALG3 p.Leu264Phe (c.790C>T) in the general population?

ALG3 p.Leu264Phe (c.790C>T) is rare (popmax 0.111%, afr) (gnomAD).

What do computational predictors say about ALG3 p.Leu264Phe (c.790C>T)?

AlphaMissense predicts likely benign (score 0.1133) — an in-silico prediction, not a clinical call.

ALG3 p.Leu264Phe

c.790C>T · rs376342417 · VCV992318

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1133 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.111%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1133	likely benign
REVEL	0.545	indeterminate
SaProt	LLR -11.01	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 2,165 bp · p 0.0031 · regional, not allelic
Overall
CADD	23.7	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 0.111% African / African-American · 83/74,928 alleles

Filtering AF 0.0915% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0844%

Overall 0.00644% 104/1,613,760 alleles · rare exomes 43/1,461,560 · genomes 61/152,200 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.111%	903
Remaining individualsnot grpmax-eligible	0.016%	6,246
Admixed American	0.015%	6,667
European (non-Finnish)	0.00017%	589,946

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: ALG3
Protein: p.Leu264Phe
Coding: c.790C>T
MANE Select: NM_005787
dbSNP: rs376342417
Type: single nucleotide variant
Location: chr3:184243933 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.05

Full ALG3 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

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ALG3 p.Arg229Cys Uncertain significance ★★ ⚠ same condition
ALG3 p.Arg27Gly Uncertain significance ★★ ⚠ same condition
ALG3 p.Arg378Cys Uncertain significance ★★ ⚠ same condition
ALG3 p.Asn83Ser Uncertain significance ★★ ⚠ same condition
ALG3 p.Cys21Gly Uncertain significance ★★ ⚠ same condition
ALG3 p.Cys21Phe Uncertain significance ★★ ⚠ same condition
ALG3 p.Cys404Trp 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/alg3-p-leu264phe (accessed [today's date]).

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