Is ALG11 p.Ser336Leu (c.1007C>T) pathogenic?

ALG11 p.Ser336Leu (c.1007C>T) is classified Uncertain significance in ALG11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-05). AlphaMissense: likely benign (0.0643); Very rare (popmax 0.00364%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ALG11 p.Ser336Leu (c.1007C>T)?

ALG11 p.Ser336Leu (c.1007C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ALG11 p.Ser336Leu (c.1007C>T) in the general population?

ALG11 p.Ser336Leu (c.1007C>T) is very rare (popmax 0.00364%, nfe) (gnomAD).

What do computational predictors say about ALG11 p.Ser336Leu (c.1007C>T)?

AlphaMissense predicts likely benign (score 0.0643) — an in-silico prediction, not a clinical call.

ALG11 p.Ser336Leu

c.1007C>T · VCV3383834

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0643 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00364%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0643	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -3.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.92, phastCons 0.69
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.068 · regional, not allelic
Overall
CADD	18.77	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

Grpmax group 0.00364% European (non-Finnish) · 43/1,180,046 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00279% 45/1,614,076 alleles · very rare exomes 44/1,461,878 · genomes 1/152,198 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00364%	27,443
Finnishnot grpmax-eligible	0.00312%	32,012

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: ALG11
Protein: p.Ser336Leu
Coding: c.1007C>T
MANE Select: NM_001004127
Type: single nucleotide variant
Location: chr13:52024737 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.40

Full ALG11 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

ALG11 p.Ser336= Likely benign ★ same residue
ALG11 p.Asp174Glu Uncertain significance ★★ ⚠ same condition
ALG11 p.Gln166Arg Uncertain significance ★★ ⚠ same condition
ALG11 p.Glu387Ala Uncertain significance ★★ ⚠ same condition
ALG11 p.Glu5Gly Uncertain significance ★★ ⚠ same condition
ALG11 p.Gly103Ser Uncertain significance ★★ ⚠ same condition
ALG11 p.Leu424Val Uncertain significance ★★ ⚠ same condition
ALG11 p.Thr275Ala 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/alg11-p-ser336leu (accessed [today's date]).

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