Is CRELD1 p.Phe389Ile (c.1165T>A) pathogenic?

CRELD1 p.Phe389Ile (c.1165T>A) is classified Uncertain significance in CRELD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely pathogenic (0.9476); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with CRELD1 p.Phe389Ile (c.1165T>A)?

CRELD1 p.Phe389Ile (c.1165T>A) is associated with Inborn genetic diseases (ClinVar).

How common is CRELD1 p.Phe389Ile (c.1165T>A) in the general population?

CRELD1 p.Phe389Ile (c.1165T>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CRELD1 p.Phe389Ile (c.1165T>A)?

AlphaMissense predicts likely pathogenic (score 0.9476) — an in-silico prediction, not a clinical call.

CRELD1 p.Phe389Ile

c.1165T>A · VCV4006793

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9476 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9476	likely pathogenic
REVEL	0.258	benign-leaning
SaProt	LLR -5.83	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 10 kb · p 0.081 · regional, not allelic
Overall
CADD	28.8	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

Grpmax group 0.00133% African / African-American · 1/75,042 alleles

Overall 6.84e-05% 1/1,461,086 alleles · very rare

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: CRELD1
Protein: p.Phe389Ile
Coding: c.1165T>A
MANE Select: NM_001077415
Type: single nucleotide variant
Location: chr3:9944481 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRELD1 c.460+1G>A Likely pathogenic ★★ same condition
CRELD1 p.Arg175Gln Uncertain significance ★★ ⚠ same condition
CRELD1 p.Cys221Arg Uncertain significance ★★ ⚠ same condition
CRELD1 p.Glu78Gln Uncertain significance ★★ ⚠ same condition
CRELD1 p.Gly164Ser Uncertain significance ★★ ⚠ same condition
CRELD1 p.Gly167Arg Uncertain significance ★★ ⚠ same condition
CRELD1 p.Gly283Arg Uncertain significance ★★ ⚠ same condition
CRELD1 p.Lys418Glu Uncertain significance ★★ ⚠ same condition

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-phe389ile (accessed [today's date]).

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