Is ERC1 p.Arg867Thr (c.2600G>C) pathogenic?

ERC1 p.Arg867Thr (c.2600G>C) is classified Uncertain significance in ERC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: likely pathogenic (0.6383); Absent from gnomAD v4.1.

How common is ERC1 p.Arg867Thr (c.2600G>C) in the general population?

ERC1 p.Arg867Thr (c.2600G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERC1 p.Arg867Thr (c.2600G>C)?

AlphaMissense predicts likely pathogenic (score 0.6383) — an in-silico prediction, not a clinical call.

ERC1 p.Arg867Thr

c.2600G>C · VCV4665069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6383 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6383	likely pathogenic
REVEL	0.182	moderately benign-leaning
SaProt	LLR -11.26	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 462 kb · p 5.7e-05 · regional, not allelic
Overall
CADD	27.1	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: ERC1
Protein: p.Arg867Thr
Coding: c.2600G>C
MANE Select: NM_178040
Type: single nucleotide variant
Location: chr12:1263146 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 75.64

Full ERC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERC1 p.Ser393= Benign ★★ same type
ERC1 c.3214-1G>A Uncertain significance ★ same type
ERC1 p.Ala1058Val Uncertain significance ★ ⚠ same type
ERC1 p.Ala199Thr Uncertain significance ★ ⚠ same type
ERC1 p.Ala260Glu Uncertain significance ★ ⚠ same type
ERC1 p.Ala5Ser Uncertain significance ★ ⚠ same type
ERC1 p.Ala621Thr Uncertain significance ★ ⚠ same type
ERC1 p.Ala682Ser 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/erc1-p-arg867thr (accessed [today's date]).

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