Is CREG1 p.Val62Glu (c.185T>A) pathogenic?

CREG1 p.Val62Glu (c.185T>A) is classified Uncertain significance in CREG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-23). AlphaMissense: likely pathogenic (0.9574); Absent from gnomAD v4.1.

How common is CREG1 p.Val62Glu (c.185T>A) in the general population?

CREG1 p.Val62Glu (c.185T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CREG1 p.Val62Glu (c.185T>A)?

AlphaMissense predicts likely pathogenic (score 0.9574) — an in-silico prediction, not a clinical call.

CREG1 p.Val62Glu

c.185T>A · VCV3497009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9574 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9574	likely pathogenic · top 4% in CREG1
REVEL	0.571	indeterminate
SaProt	LLR -12.73	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.9	GERP 0.48, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 11 kb · p 0.16 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: CREG1
Protein: p.Val62Glu
Coding: c.185T>A
MANE Select: NM_003851
Type: single nucleotide variant
Location: chr1:167553557 (GRCh38)
Gene constraint: LOEUF 1.795 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.08 · 1 PDB
Residue 62: an α-helix

Full CREG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CREG1 p.Ala11Val Uncertain significance ★ ⚠ same type
CREG1 p.Ala130Ser Uncertain significance ★ ⚠ same type
CREG1 p.Ala15Thr Uncertain significance ★ ⚠ same type
CREG1 p.Ala18Ser Uncertain significance ★ ⚠ same type
CREG1 p.Ala23Val Uncertain significance ★ ⚠ same type
CREG1 p.Ala29Ser Uncertain significance ★ ⚠ same type
CREG1 p.Ala56Glu Uncertain significance ★ ⚠ same type
CREG1 p.Ala70Ser 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/creg1-p-val62glu (accessed [today's date]).

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