Is ERMARD p.Leu530Pro (c.1589T>C) pathogenic?

ERMARD p.Leu530Pro (c.1589T>C) is classified Benign/Likely benign in ERMARD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-18). AlphaMissense: ambiguous (0.5616); Rare (popmax 0.614%, afr).

How common is ERMARD p.Leu530Pro (c.1589T>C) in the general population?

ERMARD p.Leu530Pro (c.1589T>C) is rare (popmax 0.614%, afr) (gnomAD).

What do computational predictors say about ERMARD p.Leu530Pro (c.1589T>C)?

AlphaMissense predicts ambiguous (score 0.5616) — an in-silico prediction, not a clinical call.

ERMARD p.Leu530Pro

c.1589T>C · rs141119961 · VCV678368

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.5616 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.614%, afr)

Computational evidence

Protein change
AlphaMissense	0.5616	ambiguous
REVEL	0.442	indeterminate
SaProt	LLR -10.38	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 30 kb · p 0.34 · regional, not allelic
Overall
CADD	22.3	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 0.614% African / African-American · 461/75,050 alleles

Filtering AF 0.568% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.55%

Overall 0.0359% 579/1,614,188 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.614%	163
Middle Eastern	0.115%	866
Remaining individualsnot grpmax-eligible	0.0544%	1,838
Admixed American	0.0333%	3,001
European (non-Finnish)	0.00475%	21,072
South Asian	0.0011%	91,080

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.Leu530Pro
Coding: c.1589T>C
MANE Select: NM_018341
dbSNP: rs141119961
Type: single nucleotide variant
Location: chr6:169776523 (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.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
ERMARD p.Arg571Trp 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-leu530pro (accessed [today's date]).

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