Is ERGIC1 p.Val98Glu (c.293T>A) pathogenic?

ERGIC1 p.Val98Glu (c.293T>A) is classified Pathogenic in ERGIC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-07-31). AlphaMissense: likely pathogenic (0.9769); Absent from gnomAD v4.1; Associated with arthrogryposis multiplex congenita 2, neurogenic type.

What condition is associated with ERGIC1 p.Val98Glu (c.293T>A)?

ERGIC1 p.Val98Glu (c.293T>A) is associated with arthrogryposis multiplex congenita 2, neurogenic type (ClinVar).

How common is ERGIC1 p.Val98Glu (c.293T>A) in the general population?

ERGIC1 p.Val98Glu (c.293T>A) is absent from gnomAD v4.1 (gnomAD).

How is Neurogenic arthrogryposis multiplex congenita inherited?

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

What do computational predictors say about ERGIC1 p.Val98Glu (c.293T>A)?

AlphaMissense predicts likely pathogenic (score 0.9769) — an in-silico prediction, not a clinical call.

ERGIC1 p.Val98Glu

c.293T>A · rs1554112524 · VCV523093

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9769 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

arthrogryposis multiplex congenita 2, neurogenic type

Computational evidence

Protein change
AlphaMissense	0.9769	likely pathogenic ✓ concordant with ClinVar
REVEL	0.922	moderately pathogenic-leaning
SaProt	LLR -13.00	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 92 kb · p 2.9e-05 · regional, not allelic
Overall
CADD	29.3	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: ERGIC1
Protein: p.Val98Glu
Coding: c.293T>A
MANE Select: NM_001031711
dbSNP: rs1554112524
Type: single nucleotide variant
Location: chr5:172914756 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 88.96
Residue 98: a UniProt-annotated variant site (in amc2; uncertain significance)

Full ERGIC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

arthrogryposis multiplex congenita 2, neurogenic type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Neurogenic arthrogryposis multiplex congenita (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

ERGIC1 c.250+1G>A Likely pathogenic ★ same condition
ERGIC1 c.155+1G>A Uncertain significance ★ same condition
ERGIC1 p.Cys115Trp Uncertain significance ★ same condition
ERGIC1 p.Ala228Glu Uncertain significance ★ ⚠ same type
ERGIC1 p.Ala267Thr Uncertain significance ★ ⚠ same type
ERGIC1 p.Arg116Cys Uncertain significance ★ ⚠ same type
ERGIC1 p.Arg232His Uncertain significance ★ ⚠ same type
ERGIC1 p.Arg246Trp Uncertain significance ★ ⚠ same type

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/ergic1-p-val98glu (accessed [today's date]).

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