Is ERGIC3 p.Pro329Ser (c.985C>T) pathogenic?

ERGIC3 p.Pro329Ser (c.985C>T) is classified Uncertain significance in ERGIC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-25). AlphaMissense: likely pathogenic (0.987); Absent from gnomAD v4.1.

How common is ERGIC3 p.Pro329Ser (c.985C>T) in the general population?

ERGIC3 p.Pro329Ser (c.985C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERGIC3 p.Pro329Ser (c.985C>T)?

AlphaMissense predicts likely pathogenic (score 0.987) — an in-silico prediction, not a clinical call.

ERGIC3 p.Pro329Ser

c.985C>T · VCV4019451

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.987	likely pathogenic
REVEL	0.706	pathogenic-leaning
SaProt	LLR -10.90	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 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 15 kb · p 5.2e-05 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: ERGIC3
Protein: p.Pro329Ser
Coding: c.985C>T
MANE Select: NM_015966
Type: single nucleotide variant
Location: chr20:35557078 (GRCh38)
Gene constraint: LOEUF 0.781 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.05

Full ERGIC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERGIC3 c.718-4A>G Benign ★★ same type
ERGIC3 p.Leu295= Benign ★★ same type
ERGIC3 c.686-664G>A Uncertain significance ★ same type
ERGIC3 c.717+1G>A Uncertain significance ★ same type
ERGIC3 p.Arg121Gln Uncertain significance ★ ⚠ same type
ERGIC3 p.Arg163Gln Uncertain significance ★ ⚠ same type
ERGIC3 p.Arg163Trp Uncertain significance ★ ⚠ same type
ERGIC3 p.Arg167Cys 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/ergic3-p-pro329ser (accessed [today's date]).

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