Is RGR p.Pro216= (c.648A>T) pathogenic?

RGR p.Pro216= (c.648A>T) is classified Likely benign in RGR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). Very rare (popmax 0.00333%, amr).

How common is RGR p.Pro216= (c.648A>T) in the general population?

RGR p.Pro216= (c.648A>T) is very rare (popmax 0.00333%, amr) (gnomAD).

RGR p.Pro216=

c.648A>T · VCV3619928

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 -3.5	GERP -2
Overall
CADD	0.704	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,034 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,614,126 alleles · very rare exomes 2/1,461,838 · genomes 0/152,288 · joint denominator

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: RGR
Protein: p.Pro216=
Coding: c.648A>T
MANE Select: NM_001012720
Type: single nucleotide variant
Location: chr10:84257910 (GRCh38)
Structure: AlphaFold pLDDT 62.88
Residue 216: a UniProt-annotated variant site (in)

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

Similar variants

RGR c.358+1G>A Uncertain significance ★★ same type
RGR p.Ala110Thr Uncertain significance ★★ ⚠ same type
RGR p.Ala186Thr Uncertain significance ★★ ⚠ same type
RGR p.Ala217Gly Uncertain significance ★★ ⚠ same type
RGR p.Ala234Thr Uncertain significance ★★ ⚠ same type
RGR p.Ala251Thr Uncertain significance ★★ ⚠ same type
RGR p.Ala251Val Uncertain significance ★★ ⚠ same type
RGR p.Ala61Val 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/rgr-p-pro216 (accessed [today's date]).

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