Is CELSR1 p.Val1699= (c.5097C>T) pathogenic?

CELSR1 p.Val1699= (c.5097C>T) is classified Likely benign in CELSR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-01). Ultra-rare (popmax 0.0247%, nfe).

How common is CELSR1 p.Val1699= (c.5097C>T) in the general population?

CELSR1 p.Val1699= (c.5097C>T) is ultra-rare (popmax 0.0247%, nfe) (gnomAD).

CELSR1 p.Val1699=

c.5097C>T · rs367960136 · VCV2653330

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0247%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.8	GERP -3.8
Overall
CADD	0.433	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0247% European (non-Finnish) · 291/1,179,812 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.0224% 361/1,613,416 alleles · ultra-rare exomes 339/1,461,224 · genomes 22/152,192 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0939%	1,064
European (non-Finnish)grpmax	0.0247%	4,054
Remaining individualsnot grpmax-eligible	0.00801%	12,492
Admixed American	0.00333%	29,987
African / African-American	0.00267%	37,456
South Asian	0.0011%	90,964

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CELSR1
Protein: p.Val1699=
Coding: c.5097C>T
MANE Select: NM_001378328
dbSNP: rs367960136
Type: single nucleotide variant
Location: chr22:46409125 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 1699: a UniProt-annotated variant site (in lmphm9); the laminin g-like 2 domain

Full CELSR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELSR1 p.Val1699Leu Uncertain significance ★ ⚠ same residue
CELSR1 p.Ala2442Val Uncertain significance ★★ ⚠ same type
CELSR1 p.Ala2955Thr Uncertain significance ★★ ⚠ same type
CELSR1 p.Ala396Ser Uncertain significance ★★ ⚠ same type
CELSR1 p.Ala617Ser Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1323Gln Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1379His Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1643Gln 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/celsr1-p-val1699 (accessed [today's date]).

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