Is ERMARD p.Phe266Leu (c.796T>C) pathogenic?

ERMARD p.Phe266Leu (c.796T>C) is classified Uncertain significance in ERMARD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). AlphaMissense: likely pathogenic (0.8908); Absent from gnomAD v4.1.

How common is ERMARD p.Phe266Leu (c.796T>C) in the general population?

ERMARD p.Phe266Leu (c.796T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERMARD p.Phe266Leu (c.796T>C)?

AlphaMissense predicts likely pathogenic (score 0.8908) — an in-silico prediction, not a clinical call.

ERMARD p.Phe266Leu

c.796T>C · rs2537441589 · VCV3021970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8908 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8908	likely pathogenic · top 4% in ERMARD
REVEL	0.216	benign-leaning
SaProt	LLR -7.28	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 7.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 30 kb · p 0.34 · regional, not allelic
Overall
CADD	21.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ERMARD
Protein: p.Phe266Leu
Coding: c.796T>C
MANE Select: NM_018341
dbSNP: rs2537441589
Type: single nucleotide variant
Location: chr6:169760695 (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-phe266leu (accessed [today's date]).

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