Is ERMARD p.Pro273Leu (c.818C>T) pathogenic?

ERMARD p.Pro273Leu (c.818C>T) is classified Uncertain significance in ERMARD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-05). AlphaMissense: likely benign (0.2312); Very rare (popmax 0.00401%, afr).

How common is ERMARD p.Pro273Leu (c.818C>T) in the general population?

ERMARD p.Pro273Leu (c.818C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about ERMARD p.Pro273Leu (c.818C>T)?

AlphaMissense predicts likely benign (score 0.2312) — an in-silico prediction, not a clinical call.

ERMARD p.Pro273Leu

c.818C>T · rs905901498 · VCV2603206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2312 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2312	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -10.57	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.8	GERP 4.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 30 kb · p 0.34 · regional, not allelic
Overall
CADD	24.9	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 0.00401% African / African-American · 3/74,838 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,613,496 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,946
European (non-Finnish)	8.48e-05%	1,179,792

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.Pro273Leu
Coding: c.818C>T
MANE Select: NM_018341
dbSNP: rs905901498
Type: single nucleotide variant
Location: chr6:169760717 (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.Pro273= Benign/Likely benign ★★ 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-pro273leu (accessed [today's date]).

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