Is EMC4 p.Arg108Ter (c.322C>T) pathogenic?

EMC4 p.Arg108Ter (c.322C>T) is classified Uncertain significance in EMC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-02-16). Very rare (popmax 0.00267%, afr).

How common is EMC4 p.Arg108Ter (c.322C>T) in the general population?

EMC4 p.Arg108Ter (c.322C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

EMC4 p.Arg108Ter

c.322C>T · rs779743332 · VCV285886

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 5
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -4.1, phastCons 0.95
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,888 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000372% 6/1,613,788 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,444
European (non-Finnish)	0.000339%	294,967

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: EMC4
Protein: p.Arg108Ter
Coding: c.322C>T
MANE Select: NM_016454
dbSNP: rs779743332
Type: single nucleotide variant
Location: chr15:34227813 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI 0.34 (gnomAD)
Structure: AlphaFold pLDDT 67.65 · 9 PDB
Residue 108: an α-helix

Full EMC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMC4 p.Ala3Val Uncertain significance ★ ⚠ same type
EMC4 p.Arg68His Uncertain significance ★ ⚠ same type
EMC4 p.Gly35Asp Uncertain significance ★ ⚠ same type
EMC4 p.Ile116Phe Uncertain significance ★ ⚠ same type
EMC4 p.Ile19Thr Uncertain significance ★ ⚠ same type
EMC4 p.Lys129Asn Uncertain significance ★ ⚠ same type
EMC4 p.Phe85Leu Uncertain significance ★ ⚠ same type
EMC4 p.Pro171His 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/emc4-p-arg108ter (accessed [today's date]).

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