Is CRELD1 p.Ser112Ile (c.335G>T) pathogenic?

CRELD1 p.Ser112Ile (c.335G>T) is classified Uncertain significance in CRELD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-03). AlphaMissense: ambiguous (0.5121); Absent from gnomAD v4.1; Associated with CRELD1-related disorder.

What condition is associated with CRELD1 p.Ser112Ile (c.335G>T)?

CRELD1 p.Ser112Ile (c.335G>T) is associated with CRELD1-related disorder (ClinVar).

How common is CRELD1 p.Ser112Ile (c.335G>T) in the general population?

CRELD1 p.Ser112Ile (c.335G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRELD1 p.Ser112Ile (c.335G>T)?

AlphaMissense predicts ambiguous (score 0.5121) — an in-silico prediction, not a clinical call.

CRELD1 p.Ser112Ile

c.335G>T · VCV3344624

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5121 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

CRELD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.5121	ambiguous
REVEL	0.103	moderately benign-leaning
SaProt	LLR -10.54	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 0.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 10 kb · p 0.081 · regional, not allelic
Overall
CADD	22.5	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: CRELD1
Protein: p.Ser112Ile
Coding: c.335G>T
MANE Select: NM_001077415
Type: single nucleotide variant
Location: chr3:9937639 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.68

Full CRELD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CRELD1-related disorder

Similar variants

CRELD1 c.1049-343G>C Uncertain significance same condition
CRELD1 c.1049-419C>A Uncertain significance same condition
CRELD1 p.Gly179Arg Uncertain significance ⚠ same condition
CRELD1 p.Leu115Met Uncertain significance ⚠ same condition
CRELD1 p.Glu360= Likely benign same condition
CRELD1 c.460+1G>A Likely pathogenic ★★ same type
CRELD1 c.1049-283C>T Uncertain significance ★★ same type
CRELD1 c.1049-376T>G 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/creld1-p-ser112ile (accessed [today's date]).

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