Is CELSR2 p.Ser2170= (c.6510C>T) pathogenic?

CELSR2 p.Ser2170= (c.6510C>T) is classified Likely benign in CELSR2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-07). Rare (popmax 0.14%, nfe).

How common is CELSR2 p.Ser2170= (c.6510C>T) in the general population?

CELSR2 p.Ser2170= (c.6510C>T) is rare (popmax 0.14%, nfe) (gnomAD).

CELSR2 p.Ser2170=

c.6510C>T · rs142255122 · VCV1533877

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.14%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.9	GERP -3.2
Overall
CADD	4.659	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.14% European (non-Finnish) · 1,645/1,176,578 alleles

Filtering AF 0.134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.132%

Overall 0.117% 1,887/1,609,442 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.658%	152
European (non-Finnish)grpmax	0.14%	715
Remaining individualsnot grpmax-eligible	0.137%	732
Ashkenazi Jewishnot grpmax-eligible	0.119%	841
South Asian	0.0959%	1,043
Admixed American	0.0251%	3,989
Middle Eastern	0.0165%	6,046
African / African-American	0.0133%	7,497
East Asian	0.00447%	22,356
Finnishnot grpmax-eligible	0.00156%	63,924

Amish 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: CELSR2
Protein: p.Ser2170=
Coding: c.6510C>T
MANE Select: NM_001408
dbSNP: rs142255122
Type: single nucleotide variant
Location: chr1:109268887 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)

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

Similar variants

CELSR2 p.Ser2170Tyr Uncertain significance ★ ⚠ same residue
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

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-ser2170 (accessed [today's date]).

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