Is RPRD2 p.Ser247Arg (c.739A>C) pathogenic?

RPRD2 p.Ser247Arg (c.739A>C) is classified Uncertain significance in RPRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-16). AlphaMissense: likely pathogenic (0.9986); Very rare (popmax 0.00017%, nfe).

How common is RPRD2 p.Ser247Arg (c.739A>C) in the general population?

RPRD2 p.Ser247Arg (c.739A>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about RPRD2 p.Ser247Arg (c.739A>C)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

RPRD2 p.Ser247Arg

c.739A>C · rs2525955357 · VCV2261885

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic · top 3% in RPRD2
REVEL	0.368	indeterminate
SaProt	LLR -7.98	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 54 kb · p 1.7e-14 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,177,284 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000138% 2/1,451,982 alleles · very rare

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: RPRD2
Protein: p.Ser247Arg
Coding: c.739A>C
MANE Select: NM_015203
dbSNP: rs2525955357
Type: single nucleotide variant
Location: chr1:150446270 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 48.32 · 3 PDB

Full RPRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RPRD2 p.Glu195= Benign ★★ same type
RPRD2 p.Ala1083Ser Uncertain significance ★ ⚠ same type
RPRD2 p.Ala1145Pro Uncertain significance ★ ⚠ same type
RPRD2 p.Ala1149Val Uncertain significance ★ ⚠ same type
RPRD2 p.Ala1165Val Uncertain significance ★ ⚠ same type
RPRD2 p.Ala1251Thr Uncertain significance ★ ⚠ same type
RPRD2 p.Ala140Val Uncertain significance ★ ⚠ same type
RPRD2 p.Ala442Pro 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/rprd2-p-ser247arg (accessed [today's date]).

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