Is CRMP1 p.Pro584Ser (c.1750C>T) pathogenic?

CRMP1 p.Pro584Ser (c.1750C>T) is classified Uncertain significance in CRMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-12). AlphaMissense: likely benign (0.1567); Ultra-rare (popmax 0.0283%, amr).

How common is CRMP1 p.Pro584Ser (c.1750C>T) in the general population?

CRMP1 p.Pro584Ser (c.1750C>T) is ultra-rare (popmax 0.0283%, amr) (gnomAD).

What do computational predictors say about CRMP1 p.Pro584Ser (c.1750C>T)?

AlphaMissense predicts likely benign (score 0.1567) — an in-silico prediction, not a clinical call.

CRMP1 p.Pro584Ser

c.1750C>T · VCV3836428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1567 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0283%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1567	likely benign
REVEL	0.388	indeterminate
SaProt	LLR -9.91	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 71 kb · p 8.4e-10 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P470S vs ClinVar P584S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0283% Admixed American · 17/60,026 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00539% 87/1,614,236 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0283%	3,531
European (non-Finnish)	0.00559%	17,879
Remaining individualsnot grpmax-eligible	0.0032%	31,256
African / African-American	0.00266%	37,534

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: CRMP1
Protein: p.Pro584Ser
Coding: c.1750C>T
MANE Select: NM_001014809
Type: single nucleotide variant
Location: chr4:5828542 (GRCh38)
Gene constraint: LOEUF 0.44 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.46 · 1 PDB

Full CRMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRMP1 p.Pro584Leu Uncertain significance ★ ⚠ same residue
CRMP1 c.820+8A>G Benign ★★ same type
CRMP1 c.964-8T>C Benign ★★ same type
CRMP1 p.Ala357= Benign ★★ same type
CRMP1 p.Gly261Arg Benign ★★ same type
CRMP1 p.Val524= Benign ★★ same type
CRMP1 c.381+2933T>C Uncertain significance ★ same type
CRMP1 p.Ala174Val 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/crmp1-p-pro584ser (accessed [today's date]).

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