Is GRHPR p.Arg245Ser (c.735G>T) pathogenic?

GRHPR p.Arg245Ser (c.735G>T) is classified Uncertain significance in GRHPR (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-01). AlphaMissense: likely pathogenic (0.9845); Absent from gnomAD v4.1.

How common is GRHPR p.Arg245Ser (c.735G>T) in the general population?

GRHPR p.Arg245Ser (c.735G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRHPR p.Arg245Ser (c.735G>T)?

AlphaMissense predicts likely pathogenic (score 0.9845) — an in-silico prediction, not a clinical call.

GRHPR p.Arg245Ser

c.735G>T · rs2118890222 · VCV1314885

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9845 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9845	likely pathogenic · top 2% in GRHPR
REVEL	0.865	moderately pathogenic-leaning
SaProt	LLR -14.38	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.28	acceptor loss at this position · masked 0 · deltas
Pangolin	Δ0.29	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4	GERP 0.09, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 14 kb · p 0.0084 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GRHPR
Protein: p.Arg245Ser
Coding: c.735G>T
MANE Select: NM_012203
dbSNP: rs2118890222
Type: single nucleotide variant
Location: chr9:37432008 (GRCh38)
Gene constraint: LOEUF 1.313 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.80 · 4 PDB
Residue 245: a binding site

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

Similar variants

GRHPR c.404+5G>A Likely pathogenic ★★ same type
GRHPR c.493+2T>A Pathogenic/Likely pathogenic ★★ same type
GRHPR c.494-2A>G Pathogenic/Likely pathogenic ★★ same type
GRHPR c.734+1G>A Pathogenic/Likely pathogenic ★★ same type
GRHPR c.735-1G>A Pathogenic/Likely pathogenic ★★ same type
GRHPR c.83+1G>C Pathogenic/Likely pathogenic ★★ same type
GRHPR c.84-2A>G Pathogenic ★★ same type
GRHPR c.865+1G>A Pathogenic/Likely pathogenic ★★ 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/grhpr-p-arg245ser (accessed [today's date]).

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