Is RGR p.Phe134= (c.402C>T) pathogenic?

RGR p.Phe134= (c.402C>T) is classified Likely benign in RGR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-26). Very rare (popmax 0.004%, afr).

How common is RGR p.Phe134= (c.402C>T) in the general population?

RGR p.Phe134= (c.402C>T) is very rare (popmax 0.004%, afr) (gnomAD).

RGR p.Phe134=

c.402C>T · rs745567392 · VCV1657690

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.3	GERP -3.6
Overall
CADD	4.584	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,930 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000496% 8/1,614,002 alleles · very rare exomes 6/1,461,808 · genomes 2/152,194 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,977
Admixed American	0.00167%	60,006
Remaining individualsnot grpmax-eligible	0.0016%	62,476
Finnishnot grpmax-eligible	0.00156%	63,970
South Asian	0.0011%	91,088
European (non-Finnish)	8.47e-05%	1,180,043

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.Phe134=
Coding: c.402C>T
MANE Select: NM_001012720
dbSNP: rs745567392
Type: single nucleotide variant
Location: chr10:84252900 (GRCh38)
Structure: AlphaFold pLDDT 62.88
Residue 134: the 'disordered' region

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

Similar variants

RGL4 p.Ala134Thr Uncertain significance ★ ⚠ same residue
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

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-phe134 (accessed [today's date]).

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