Is ALG11 p.Thr435Ser (c.1304C>G) pathogenic?

ALG11 p.Thr435Ser (c.1304C>G) is classified Uncertain significance in ALG11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-01). AlphaMissense: likely benign (0.2451); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ALG11 p.Thr435Ser (c.1304C>G)?

ALG11 p.Thr435Ser (c.1304C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ALG11 p.Thr435Ser (c.1304C>G) in the general population?

ALG11 p.Thr435Ser (c.1304C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG11 p.Thr435Ser (c.1304C>G)?

AlphaMissense predicts likely benign (score 0.2451) — an in-silico prediction, not a clinical call.

ALG11 p.Thr435Ser

c.1304C>G · VCV3520661

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2451 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2451	likely benign
REVEL	0.612	indeterminate
SaProt	LLR -11.26	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.068 · regional, not allelic
Overall
CADD	26.0	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

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: ALG11
Protein: p.Thr435Ser
Coding: c.1304C>G
MANE Select: NM_001004127
Type: single nucleotide variant
Location: chr13:52028415 (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

UTP14C p.Asn435Lys Uncertain significance ★ ⚠ 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.Ser336Leu 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-thr435ser (accessed [today's date]).

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