Is ERMARD p.Arg571Pro (c.1712G>C) pathogenic?

ERMARD p.Arg571Pro (c.1712G>C) is classified Uncertain significance in ERMARD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-14). AlphaMissense: likely pathogenic (0.9718); Very rare (popmax 0.00223%, eas).

How common is ERMARD p.Arg571Pro (c.1712G>C) in the general population?

ERMARD p.Arg571Pro (c.1712G>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ERMARD p.Arg571Pro (c.1712G>C)?

AlphaMissense predicts likely pathogenic (score 0.9718) — an in-silico prediction, not a clinical call.

ERMARD p.Arg571Pro

c.1712G>C · rs371767163 · VCV2611737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9718 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9718	likely pathogenic · top 1% in ERMARD
REVEL	0.759	pathogenic-leaning
SaProt	LLR -14.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 30 kb · p 0.34 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,886 alleles

Overall 6.84e-05% 1/1,461,684 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.Arg571Pro
Coding: c.1712G>C
MANE Select: NM_018341
dbSNP: rs371767163
Type: single nucleotide variant
Location: chr6:169776646 (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.Arg571Gln Uncertain significance ★★ ⚠ same residue
ERMARD p.Arg571Trp 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-arg571pro (accessed [today's date]).

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