Is ERMARD p.Thr565Met (c.1694C>T) pathogenic?

ERMARD p.Thr565Met (c.1694C>T) is classified Conflicting classifications of pathogenicity in ERMARD (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-01). AlphaMissense: likely benign (0.0903); Ultra-rare (popmax 0.0231%, sas).

How common is ERMARD p.Thr565Met (c.1694C>T) in the general population?

ERMARD p.Thr565Met (c.1694C>T) is ultra-rare (popmax 0.0231%, sas) (gnomAD).

What do computational predictors say about ERMARD p.Thr565Met (c.1694C>T)?

AlphaMissense predicts likely benign (score 0.0903) — an in-silico prediction, not a clinical call.

ERMARD p.Thr565Met

c.1694C>T · rs200319641 · VCV2657148

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0903 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0903	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -8.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.95	GERP -5
Regional constraint	o/e 1.03	unconstrained · MANE · 30 kb · p 0.34 · regional, not allelic
Overall
CADD	14.42	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 0.0231% South Asian · 21/91,080 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.0107% 172/1,614,164 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0231%	4,337
Admixed American	0.0217%	4,617
European (non-Finnish)	0.0111%	9,008
Remaining individualsnot grpmax-eligible	0.008%	12,501
East Asian	0.00223%	44,884
Finnishnot grpmax-eligible	0.00156%	64,040

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.Thr565Met
Coding: c.1694C>T
MANE Select: NM_018341
dbSNP: rs200319641
Type: single nucleotide variant
Location: chr6:169776628 (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.Thr565= 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-thr565met (accessed [today's date]).

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