Is ERMARD p.Cys443= (c.1329T>C) pathogenic?

ERMARD p.Cys443= (c.1329T>C) is classified Benign/Likely benign in ERMARD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-01). Rare (popmax 0.741%, afr).

How common is ERMARD p.Cys443= (c.1329T>C) in the general population?

ERMARD p.Cys443= (c.1329T>C) is rare (popmax 0.741%, afr) (gnomAD).

ERMARD p.Cys443=

c.1329T>C · rs76173501 · VCV388446

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.741%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.37	GERP 1.3, phastCons 0.97
Overall
CADD	6.832	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.741% African / African-American · 556/75,062 alleles

Filtering AF 0.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.67%

Overall 0.0404% 652/1,614,204 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.741%	135
Admixed American	0.0716%	1,396
Remaining individualsnot grpmax-eligible	0.0624%	1,603
European (non-Finnish)	0.00119%	84,288

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.Cys443=
Coding: c.1329T>C
MANE Select: NM_018341
dbSNP: rs76173501
Type: single nucleotide variant
Location: chr6:169775281 (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.Cys443Tyr Uncertain significance ★ ⚠ same residue
ERMARD p.Ala474Val Uncertain significance ★★ ⚠ same type
ERMARD p.Arg367His Uncertain significance ★★ ⚠ same type
ERMARD p.Arg400Ser Uncertain significance ★★ ⚠ same type
ERMARD p.Arg537Gln Uncertain significance ★★ ⚠ same type
ERMARD p.Arg544Cys Uncertain significance ★★ ⚠ same type
ERMARD p.Arg569Cys Uncertain significance ★★ ⚠ same type
ERMARD p.Arg571Gln 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-cys443 (accessed [today's date]).

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