Is CELSR2 p.Ile1950= (c.5850C>T) pathogenic?

CELSR2 p.Ile1950= (c.5850C>T) is classified Likely benign in CELSR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-04). Very rare (popmax 0.00856%, nfe).

How common is CELSR2 p.Ile1950= (c.5850C>T) in the general population?

CELSR2 p.Ile1950= (c.5850C>T) is very rare (popmax 0.00856%, nfe) (gnomAD).

CELSR2 p.Ile1950=

c.5850C>T · rs777797117 · VCV1590444

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00856%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -4.2
Overall
CADD	7.428	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00856% European (non-Finnish) · 101/1,180,006 alleles

Filtering AF 0.00716% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00668%

Overall 0.00651% 105/1,613,938 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00856%	11,683
Remaining individualsnot grpmax-eligible	0.0032%	31,245
Finnishnot grpmax-eligible	0.00156%	63,962
African / African-American	0.00133%	74,908

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: CELSR2
Protein: p.Ile1950=
Coding: c.5850C>T
MANE Select: NM_001408
dbSNP: rs777797117
Type: single nucleotide variant
Location: chr1:109265857 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Residue 1950: the laminin egf-like domain; a disulfide bond

Full CELSR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELSR2 c.8338+1G>C Uncertain significance ★★ same type
CELSR2 p.Ala1114Val Uncertain significance ★★ ⚠ same type
CELSR2 p.Ala2145Thr Uncertain significance ★★ ⚠ same type
CELSR2 p.Ala2574Thr Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1171Gln Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1328His Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1400His Uncertain significance ★★ same type
CELSR2 p.Arg1978Gln 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/celsr2-p-ile1950 (accessed [today's date]).

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