Is GJC2 p.Pro384Ser (c.1150C>T) pathogenic?

GJC2 p.Pro384Ser (c.1150C>T) is classified Conflicting classifications of pathogenicity in GJC2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-08-03). AlphaMissense: likely benign (0.0697); Rare (popmax 0.341%, mid); Associated with Inborn genetic diseases.

What condition is associated with GJC2 p.Pro384Ser (c.1150C>T)?

GJC2 p.Pro384Ser (c.1150C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GJC2 p.Pro384Ser (c.1150C>T) in the general population?

GJC2 p.Pro384Ser (c.1150C>T) is rare (popmax 0.341%, mid) (gnomAD).

What do computational predictors say about GJC2 p.Pro384Ser (c.1150C>T)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

GJC2 p.Pro384Ser

c.1150C>T · rs535282333 · VCV945347

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.341%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.608	indeterminate
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2
Regional constraint	o/e 1.12	unconstrained · MANE · 621 bp · p 0.039 · regional, not allelic
Overall
CADD	1.468	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 0.341% Middle Eastern · 15/4,402 alleles

Filtering AF 0.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.17%

Overall 0.0207% 308/1,488,928 alleles · rare exomes 264/1,336,848 · genomes 44/152,080 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.341%	293
Admixed American	0.105%	957
Remaining individualsnot grpmax-eligible	0.0486%	2,056
African / African-American	0.0364%	2,747
European (non-Finnish)	0.0171%	5,845
South Asian	0.00254%	39,372
Finnishnot grpmax-eligible	0.00224%	44,574

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: GJC2
Protein: p.Pro384Ser
Coding: c.1150C>T
MANE Select: NM_020435
dbSNP: rs535282333
Type: single nucleotide variant
Location: chr1:228158908 (GRCh38)
Gene constraint: LOEUF 1.604 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 68.50
Residue 384: the 'disordered' region

Full GJC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GJC2 p.Pro384His Uncertain significance ★★ ⚠ same residue
GJC2 p.Pro384Thr Uncertain significance ★ ⚠ same residue
GJC2 p.Leu28Pro Likely pathogenic ★★ same condition
GJC2 p.Ala126Val Uncertain significance ★★ ⚠ same condition
GJC2 p.Ala184Thr Uncertain significance ★★ ⚠ same condition
GJC2 p.Ala308Val Uncertain significance ★★ ⚠ same condition
GJC2 p.Ala322Glu Uncertain significance ★★ ⚠ same condition
GJC2 p.Ala70Thr 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/gjc2-p-pro384ser (accessed [today's date]).

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