Is ERMARD p.Val188Ala (c.563T>C) pathogenic?

ERMARD p.Val188Ala (c.563T>C) is classified Conflicting classifications of pathogenicity in ERMARD (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-04-17). AlphaMissense: ambiguous (0.5246); Rare (popmax 0.181%, afr).

How common is ERMARD p.Val188Ala (c.563T>C) in the general population?

ERMARD p.Val188Ala (c.563T>C) is rare (popmax 0.181%, afr) (gnomAD).

What do computational predictors say about ERMARD p.Val188Ala (c.563T>C)?

AlphaMissense predicts ambiguous (score 0.5246) — an in-silico prediction, not a clinical call.

ERMARD p.Val188Ala

c.563T>C · rs74451194 · VCV446063

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.5246 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.181%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5246	ambiguous
REVEL	0.19	benign-leaning
SaProt	LLR -9.75	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 4, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 30 kb · p 0.34 · regional, not allelic
Overall
CADD	20.9	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 0.181% African / African-American · 136/75,028 alleles

Filtering AF 0.156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.00942% 152/1,614,036 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.181%	552
Remaining individualsnot grpmax-eligible	0.0144%	6,945
Admixed American	0.01%	9,990
European (non-Finnish)	8.47e-05%	1,179,990

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.Val188Ala
Coding: c.563T>C
MANE Select: NM_018341
dbSNP: rs74451194
Type: single nucleotide variant
Location: chr6:169759023 (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.Val188Ile Uncertain significance ★ ⚠ same residue
ERMARD p.Val188fs 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

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-val188ala (accessed [today's date]).

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