Is ERMARD p.Val464fs (c.1389del) pathogenic?

ERMARD p.Val464fs (c.1389del) is classified Uncertain significance in ERMARD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). Very rare (popmax 0.000169%, nfe).

How common is ERMARD p.Val464fs (c.1389del) in the general population?

ERMARD p.Val464fs (c.1389del) is very rare (popmax 0.000169%, nfe) (gnomAD).

ERMARD p.Val464fs

c.1389del · rs1793456549 · VCV2905574

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.47	GERP -2.2
Overall
CADD	20.4	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 0.000169% European (non-Finnish) · 2/1,179,962 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,982 alleles · very rare

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: ERMARD
Protein: p.Val464fs
Coding: c.1389del
MANE Select: NM_018341
dbSNP: rs1793456549
Type: Deletion
Location: chr6:169775340 (GRCh38)
Gene constraint: LOEUF 0.996 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.79

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

Similar variants

ERMARD p.Asp63fs Uncertain significance ★★ same type
ERMARD c.1395-11_1395-10del Likely benign ★★ same type
ERMARD c.1521-82del Uncertain significance ★ same type
ERMARD p.Ala121del Uncertain significance ★ same type
ERMARD p.Arg544fs Uncertain significance ★ same type
ERMARD p.Asp358fs Uncertain significance ★ same type
ERMARD p.Cys12fs Conflicting classifications of pathogenicity ★ same type
ERMARD p.Cys495del 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/ermard-p-val464fs (accessed [today's date]).

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