Is REN p.Asp248Glu (c.744C>A) pathogenic?

REN p.Asp248Glu (c.744C>A) is classified Conflicting classifications of pathogenicity in REN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-27). AlphaMissense: likely pathogenic (0.6298); Very rare (popmax 0.00822%, nfe); Associated with Inborn genetic diseases.

What condition is associated with REN p.Asp248Glu (c.744C>A)?

REN p.Asp248Glu (c.744C>A) is associated with Inborn genetic diseases, familial juvenile hyperuricemic nephropathy type 2, renal tubular dysgenesis (ClinVar).

How common is REN p.Asp248Glu (c.744C>A) in the general population?

REN p.Asp248Glu (c.744C>A) is very rare (popmax 0.00822%, nfe) (gnomAD).

What do computational predictors say about REN p.Asp248Glu (c.744C>A)?

AlphaMissense predicts likely pathogenic (score 0.6298) — an in-silico prediction, not a clinical call.

REN p.Asp248Glu

c.744C>A · rs747881047 · VCV294954

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6298 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00822%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6298	likely pathogenic
REVEL	0.744	pathogenic-leaning
SaProt	LLR -11.95	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -0.34, phastCons 1
Overall
CADD	22.9	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

Grpmax group 0.00822% European (non-Finnish) · 97/1,179,994 alleles

Filtering AF 0.00689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00663% 107/1,613,930 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00822%	12,165
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Admixed American	0.00333%	29,996
African / African-American	0.00267%	37,447
South Asian	0.0022%	45,540
Finnishnot grpmax-eligible	0.00156%	64,000

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.Asp248Glu
Coding: c.744C>A
MANE Select: NM_001363642 · reported on NM_000537
dbSNP: rs747881047
Type: single nucleotide variant
Location: chr1:204156751 (GRCh38)
Structure: AlphaFold pLDDT 85.00

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial juvenile hyperuricemic nephropathy type 2 renal tubular dysgenesis

Similar variants

REN c.249+1G>A Pathogenic/Likely pathogenic ★★ same condition
REN p.Arg49Ter Pathogenic/Likely pathogenic ★★ same condition
REN p.Lys139Ter Pathogenic ★★ same condition
REN p.Ala182Thr Uncertain significance ★★ ⚠ same condition
REN p.Arg119Cys Uncertain significance ★★ ⚠ same condition
REN p.Arg119His Uncertain significance ★★ ⚠ same condition
REN p.Arg387Gln Uncertain significance ★★ ⚠ same condition
REN p.Arg395Trp 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-asp248glu (accessed [today's date]).

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