Is ERGIC2 p.Val302Leu (c.904G>T) pathogenic?

ERGIC2 p.Val302Leu (c.904G>T) is classified Uncertain significance in ERGIC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely pathogenic (0.8961); Absent from gnomAD v4.1.

How common is ERGIC2 p.Val302Leu (c.904G>T) in the general population?

ERGIC2 p.Val302Leu (c.904G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERGIC2 p.Val302Leu (c.904G>T)?

AlphaMissense predicts likely pathogenic (score 0.8961) — an in-silico prediction, not a clinical call.

ERGIC2 p.Val302Leu

c.904G>T · VCV4250682

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8961 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8961	likely pathogenic
REVEL	0.307	indeterminate
SaProt	LLR -8.21	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 30 kb · p 0.0048 · regional, not allelic
Overall
CADD	32.0	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: ERGIC2
Protein: p.Val302Leu
Coding: c.904G>T
MANE Select: NM_016570
Type: single nucleotide variant
Location: chr12:29343204 (GRCh38)
Gene constraint: LOEUF 1.266 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21

Full ERGIC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERGIC2 c.572+5G>A Pathogenic ★ same type
ERGIC2 p.Ala240Ser Uncertain significance ★ ⚠ same type
ERGIC2 p.Ala283Glu Uncertain significance ★ ⚠ same type
ERGIC2 p.Arg197Cys Uncertain significance ★ ⚠ same type
ERGIC2 p.Arg277Pro Uncertain significance ★ ⚠ same type
ERGIC2 p.Arg346His Uncertain significance ★ ⚠ same type
ERGIC2 p.Asn179Ser Uncertain significance ★ ⚠ same type
ERGIC2 p.Asn356Ser 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/ergic2-p-val302leu (accessed [today's date]).

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