Is ALG13 p.Pro612Ser (c.1834C>T) pathogenic?

ALG13 p.Pro612Ser (c.1834C>T) is classified Likely benign in ALG13 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-21). AlphaMissense: likely benign (0.1274); Ultra-rare (popmax 0.0175%, nfe); Associated with developmental and epileptic encephalopathy, 36.

What condition is associated with ALG13 p.Pro612Ser (c.1834C>T)?

ALG13 p.Pro612Ser (c.1834C>T) is associated with developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Pro612Ser (c.1834C>T) in the general population?

ALG13 p.Pro612Ser (c.1834C>T) is ultra-rare (popmax 0.0175%, nfe) (gnomAD).

How is ALG13-CDG inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ALG13 p.Pro612Ser (c.1834C>T)?

AlphaMissense predicts likely benign (score 0.1274) — an in-silico prediction, not a clinical call.

ALG13 p.Pro612Ser

c.1834C>T · rs200516126 · VCV664160

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1274 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0175%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 36

Computational evidence

Protein change
AlphaMissense	0.1274	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -5.98	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 0.26	GERP 3.5
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.27 · regional, not allelic
Overall
CADD	12.16	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 0.0175% European (non-Finnish) · 157/895,042 alleles

Filtering AF 0.0152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0144%

Overall 0.0149% 180/1,209,562 alleles · ultra-rare exomes 169/1,098,009 · genomes 11/111,553 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0215%	4,658
European (non-Finnish)grpmax	0.0175%	5,701
Remaining individualsnot grpmax-eligible	0.0168%	5,949
African / African-American	0.00526%	19,015
Admixed American	0.00437%	22,875

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ALG13
Protein: p.Pro612Ser
Coding: c.1834C>T
MANE Select: NM_001099922
dbSNP: rs200516126
Type: single nucleotide variant
Location: chrX:111726913 (GRCh38)
Structure: AlphaFold pLDDT 54.42

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

Disease context

developmental and epileptic encephalopathy, 36 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG13-CDG (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy, Neonatal

Similar variants

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
ALG13 p.Ala1044Thr Uncertain significance ★★ ⚠ same condition
ALG13 p.Ala173Val 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-pro612ser (accessed [today's date]).

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