Is REN p.Thr68= (c.204A>C) pathogenic?

REN p.Thr68= (c.204A>C) is classified Benign in REN (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Common (popmax 31.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with renal tubular dysgenesis.

What condition is associated with REN p.Thr68= (c.204A>C)?

REN p.Thr68= (c.204A>C) is associated with renal tubular dysgenesis, familial juvenile hyperuricemic nephropathy type 2 (ClinVar).

REN p.Thr68=

Q: How common is REN p.Thr68= (c.204A>C) in the general population?

REN p.Thr68= (c.204A>C) is common (popmax 31.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.204A>C · rs5705 · VCV256379

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 31.7%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

renal tubular dysgenesis

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 0.11	GERP -2.5, phastCons 0.001
Overall
CADD	2.194	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31.7% African / African-American · 23,772/74,920 alleles

Filtering AF 31.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 31.3%

Overall 13.3% 214,373/1,613,772 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	31.7%	3
Middle Eastern	18.3%	5
Admixed American	17.6%	6
Ashkenazi Jewishnot grpmax-eligible	15.8%	6
Amishnot grpmax-eligible	14.7%	7
Remaining individualsnot grpmax-eligible	14.1%	7
European (non-Finnish)	12.2%	8
South Asian	11.3%	9
Finnishnot grpmax-eligible	10.9%	9
East Asian	8.4%	12

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.Thr68=
Coding: c.204A>C
MANE Select: NM_001363642 · reported on NM_000537
dbSNP: rs5705
Type: single nucleotide variant
Location: chr1:204162058 (GRCh38)
Structure: AlphaFold pLDDT 85.00

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

Disease context

renal tubular dysgenesis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial juvenile hyperuricemic nephropathy type 2

Similar variants

REN p.Thr68Ile Uncertain significance ★ ⚠ same residue
REN c.249+1G>A Pathogenic/Likely pathogenic ★★ same condition
REN p.Arg49Ter Pathogenic/Likely pathogenic ★★ same condition
REN p.Ala182Thr Uncertain significance ★★ ⚠ same condition
REN p.Arg119Cys Uncertain significance ★★ ⚠ same condition
REN p.Arg387Gln Uncertain significance ★★ ⚠ same condition
REN p.Arg395Trp Uncertain significance ★★ ⚠ same condition
REN p.Arg406Cys Uncertain significance ★★ same condition

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-thr68 (accessed [today's date]).

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