Is GRPR p.Ser168= (c.504C>T) pathogenic?

GRPR p.Ser168= (c.504C>T) is classified Likely benign in GRPR (ClinVar, Single submitter, 2 submitters; last evaluated 2018-06-29). Ultra-rare (popmax 0.0465%, nfe).

How common is GRPR p.Ser168= (c.504C>T) in the general population?

GRPR p.Ser168= (c.504C>T) is ultra-rare (popmax 0.0465%, nfe) (gnomAD).

GRPR p.Ser168=

c.504C>T · rs149768942 · VCV753760

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0465%, 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 0.13	GERP 0.064, phastCons 0.94
Overall
CADD	8.071	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0465% European (non-Finnish) · 415/892,170 alleles

Filtering AF 0.0428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0413%

Overall 0.0367% 443/1,206,278 alleles · ultra-rare exomes 427/1,094,907 · genomes 16/111,371 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0484%	2,065
European (non-Finnish)grpmax	0.0465%	2,150
African / African-American	0.00527%	18,964
Finnishnot grpmax-eligible	0.0043%	23,268

Remaining individuals 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: GRPR
Protein: p.Ser168=
Coding: c.504C>T
MANE Select: NM_005314
dbSNP: rs149768942
Type: single nucleotide variant
Location: chrX:16150395 (GRCh38)
Structure: AlphaFold pLDDT 78.78 · 4 PDB
Residue 168: an α-helix

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

Similar variants

GRPR p.Lys362= Likely benign ★★ same type
GRPR p.Thr132= Benign ★★ same type
GRPR p.Val220Ile Likely benign ★★ same type
GRPR p.Ala136Val Uncertain significance ★ ⚠ same type
GRPR p.Ala369Val Uncertain significance ★ ⚠ same type
GRPR p.Arg144Trp Uncertain significance ★ ⚠ same type
GRPR p.Arg261Gln Uncertain significance ★ ⚠ same type
GRPR p.Arg287Leu 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/grpr-p-ser168 (accessed [today's date]).

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