Is ERC1 p.Pro1048Ala (c.3142C>G) pathogenic?

ERC1 p.Pro1048Ala (c.3142C>G) is classified Uncertain significance in ERC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-01). AlphaMissense: likely benign (0.3281); Absent from gnomAD v4.1.

How common is ERC1 p.Pro1048Ala (c.3142C>G) in the general population?

ERC1 p.Pro1048Ala (c.3142C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERC1 p.Pro1048Ala (c.3142C>G)?

AlphaMissense predicts likely benign (score 0.3281) — an in-silico prediction, not a clinical call.

ERC1 p.Pro1048Ala

c.3142C>G · VCV3906089

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3281 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3281	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -13.65	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 462 kb · p 5.7e-05 · regional, not allelic
Overall
CADD	25.4	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.Pro1048Ala
Coding: c.3142C>G
MANE Select: NM_178040
Type: single nucleotide variant
Location: chr12:1444679 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 75.64
Residue 1048: the fip-rbd domain

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-pro1048ala (accessed [today's date]).

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