Is REN p.Arg395= (c.1183C>A) pathogenic?

REN p.Arg395= (c.1183C>A) is classified Likely benign in REN (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-03). Ultra-rare (popmax 0.0395%, sas).

How common is REN p.Arg395= (c.1183C>A) in the general population?

REN p.Arg395= (c.1183C>A) is ultra-rare (popmax 0.0395%, sas) (gnomAD).

REN p.Arg395=

c.1183C>A · rs773404995 · VCV741958

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0395%, sas)

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 8.7	GERP 1.2, phastCons 1
Overall
CADD	12.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0395% South Asian · 36/91,078 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.00316% 51/1,614,084 alleles · ultra-rare exomes 47/1,461,830 · genomes 4/152,254 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0395%	2,530
Remaining individualsnot grpmax-eligible	0.016%	6,249
European (non-Finnish)	0.000424%	236,010

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: REN
Protein: p.Arg395=
Coding: c.1183C>A
MANE Select: NM_000537
dbSNP: rs773404995
Type: single nucleotide variant
Location: chr1:204155054 (GRCh38)
Structure: AlphaFold pLDDT 85.00

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

Similar variants

REN p.Arg395Trp Uncertain significance ★★ ⚠ same residue
REN p.Arg395Gln Uncertain significance ★ ⚠ same residue
REN p.Arg395Leu Uncertain significance ★ ⚠ same residue
REN c.249+1G>A Pathogenic/Likely pathogenic ★★ same type
REN p.Arg49Ter Pathogenic/Likely pathogenic ★★ same type
REN p.Lys139Ter Pathogenic ★★ same type
REN p.Ala182Thr Uncertain significance ★★ ⚠ same type
REN p.Arg119Cys 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/ren-p-arg395 (accessed [today's date]).

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