Is ERMARD p.Arg286Lys (c.857G>A) pathogenic?

ERMARD p.Arg286Lys (c.857G>A) is classified Uncertain significance in ERMARD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely benign (0.2119); Absent from gnomAD v4.1.

How common is ERMARD p.Arg286Lys (c.857G>A) in the general population?

ERMARD p.Arg286Lys (c.857G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERMARD p.Arg286Lys (c.857G>A)?

AlphaMissense predicts likely benign (score 0.2119) — an in-silico prediction, not a clinical call.

ERMARD p.Arg286Lys

c.857G>A · rs756037767 · VCV2097169

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2119 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,603,260)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2119	likely benign
REVEL	0.285	benign-leaning
SaProt	LLR -4.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.92	donor loss · deltas
Pangolin	Δ0.64	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 4.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 30 kb · p 0.34 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,603,260). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ERMARD
Protein: p.Arg286Lys
Coding: c.857G>A
MANE Select: NM_018341
dbSNP: rs756037767
Type: single nucleotide variant
Location: chr6:169760756 (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-arg286lys (accessed [today's date]).

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