Is ALG13 p.Pro1005Ser (c.3013C>T) pathogenic?

ALG13 p.Pro1005Ser (c.3013C>T) is classified Pathogenic/Likely pathogenic in ALG13 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2022-04-01). AlphaMissense: likely benign (0.1503); Absent from gnomAD v4.1; Associated with Neurodevelopmental delay.

What condition is associated with ALG13 p.Pro1005Ser (c.3013C>T)?

ALG13 p.Pro1005Ser (c.3013C>T) is associated with Neurodevelopmental delay, developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Pro1005Ser (c.3013C>T) in the general population?

ALG13 p.Pro1005Ser (c.3013C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG13 p.Pro1005Ser (c.3013C>T)?

AlphaMissense predicts likely benign (score 0.1503) — an in-silico prediction, not a clinical call.

ALG13 p.Pro1005Ser

c.3013C>T · rs1945385727 · VCV1344833

Pathogenic/Likely pathogenic No assertion criteria

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1503 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Neurodevelopmental delay

Computational evidence

Protein change
AlphaMissense	0.1503	likely benign ⚠ discordant with ClinVar
REVEL	0.166	moderately benign-leaning
SaProt	LLR -7.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.23	gain · loss 0.09 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.8	GERP 1.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 2,374 bp · p 0.62 · regional, not allelic
Overall
CADD	21.6	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: ALG13
Protein: p.Pro1005Ser
Coding: c.3013C>T
MANE Select: NM_001099922
dbSNP: rs1945385727
Type: single nucleotide variant
Location: chrX:111757627 (GRCh38)
Structure: AlphaFold pLDDT 54.42

Full ALG13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Neurodevelopmental delay — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 36

Similar variants

ALG13 p.Pro1005= Likely benign ★ same residue
ALG13 p.Pro1005Thr Uncertain significance ★ ⚠ same residue
ALG13 p.Asn107Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
ALG13 c.2458-1G>A Uncertain significance ★★ same condition
ALG13 c.2695+4G>A Uncertain significance ★★ same condition
ALG13 c.2932+6T>C Uncertain significance ★★ same condition
ALG13 c.834+3A>G Uncertain significance ★★ same condition
ALG13 c.932+2T>C 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/alg13-p-pro1005ser (accessed [today's date]).

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