Is ERN2 p.Tyr601= (c.1803C>T) pathogenic?

ERN2 p.Tyr601= (c.1803C>T) is classified Likely benign in ERN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Very rare (popmax 0.00534%, afr).

How common is ERN2 p.Tyr601= (c.1803C>T) in the general population?

ERN2 p.Tyr601= (c.1803C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

ERN2 p.Tyr601=

c.1803C>T · rs771033285 · VCV2646327

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.92 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5	GERP -3.7
Overall
CADD	0.337	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,898 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000806% 13/1,613,894 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,724
European (non-Finnish)	0.000763%	131,105

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: ERN2
Protein: p.Tyr601=
Coding: c.1803C>T
MANE Select: NM_033266
dbSNP: rs771033285
Type: single nucleotide variant
Location: chr16:23695116 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.91 · 2 PDB
Residue 601: the protein kinase domain

Full ERN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERN2 p.Arg868Ter Uncertain significance ★★ same type
ERN2 p.Val69Ile Benign ★★ ⚠ same type
ERN2 p.Ala22Val Uncertain significance ★ ⚠ same type
ERN2 p.Ala318Asp Uncertain significance ★ ⚠ same type
ERN2 p.Ala395Val Uncertain significance ★ ⚠ same type
ERN2 p.Ala4Thr Uncertain significance ★ ⚠ same type
ERN2 p.Ala760Thr Uncertain significance ★ ⚠ same type
ERN2 p.Ala80Thr 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/ern2-p-tyr601 (accessed [today's date]).

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