Is RCC2 p.Ser504Arg (c.1512T>A) pathogenic?

RCC2 p.Ser504Arg (c.1512T>A) is classified Uncertain significance in RCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely pathogenic (0.5738); Absent from gnomAD v4.1.

How common is RCC2 p.Ser504Arg (c.1512T>A) in the general population?

RCC2 p.Ser504Arg (c.1512T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RCC2 p.Ser504Arg (c.1512T>A)?

AlphaMissense predicts likely pathogenic (score 0.5738) — an in-silico prediction, not a clinical call.

RCC2 p.Ser504Arg

c.1512T>A · rs2526305842 · VCV3152695

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5738 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5738	likely pathogenic
REVEL	0.104	moderately benign-leaning
SaProt	LLR -10.51	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4	GERP -3.2
Regional constraint	o/e 0.56	unconstrained · MANE · 12 kb · p 1.6e-15 · regional, not allelic
Overall
CADD	4.166	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

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: RCC2
Protein: p.Ser504Arg
Coding: c.1512T>A
MANE Select: NM_018715
dbSNP: rs2526305842
Type: single nucleotide variant
Location: chr1:17409147 (GRCh38)
Gene constraint: LOEUF 0.508 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 88.97 · 1 PDB
Residue 504: the 'disordered' region

Full RCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RCC2 p.Ala146Glu Uncertain significance ★ ⚠ same type
RCC2 p.Ala490Thr Uncertain significance ★ ⚠ same type
RCC2 p.Ala6Val Uncertain significance ★ ⚠ same type
RCC2 p.Ala78Thr Uncertain significance ★ ⚠ same type
RCC2 p.Ala7Gly Uncertain significance ★ ⚠ same type
RCC2 p.Ala9Thr Uncertain significance ★ ⚠ same type
RCC2 p.Arg149Gln Uncertain significance ★ ⚠ same type
RCC2 p.Arg151Trp 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/rcc2-p-ser504arg (accessed [today's date]).

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