Is REN p.Ser135Tyr (c.404C>A) pathogenic?

REN p.Ser135Tyr (c.404C>A) is classified Pathogenic in REN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2011-01-15). AlphaMissense: likely pathogenic (0.9476); Absent from gnomAD v4.1; Associated with renal tubular dysgenesis.

What condition is associated with REN p.Ser135Tyr (c.404C>A)?

REN p.Ser135Tyr (c.404C>A) is associated with renal tubular dysgenesis (ClinVar).

How common is REN p.Ser135Tyr (c.404C>A) in the general population?

REN p.Ser135Tyr (c.404C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about REN p.Ser135Tyr (c.404C>A)?

AlphaMissense predicts likely pathogenic (score 0.9476) — an in-silico prediction, not a clinical call.

REN p.Ser135Tyr

c.404C>A · rs397514691 · VCV50211

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9476 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal tubular dysgenesis

Computational evidence

Protein change
AlphaMissense	0.9476	likely pathogenic ✓ concordant with ClinVar · top 10% in REN
REVEL	0.894	moderately pathogenic-leaning
SaProt	LLR -15.97	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.20	acceptor loss, 7 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	26.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: REN
Protein: p.Ser135Tyr
Coding: c.404C>A
MANE Select: NM_001363642 · reported on NM_000537
dbSNP: rs397514691
Type: single nucleotide variant
Location: chr1:204160648 (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

Similar variants

REN p.Arg49Ter Pathogenic/Likely pathogenic ★★ same condition
REN p.Gln85His Uncertain significance ★★ ⚠ same condition
REN p.Glu89Asp Uncertain significance ★★ ⚠ same condition
REN p.Gly240Arg Uncertain significance ★★ ⚠ same condition
REN p.Gly273Arg Uncertain significance ★★ ⚠ same condition
REN c.373+44C>G Benign ★★ same condition
REN c.492+17T>G Benign ★★ same condition
REN c.492+3A>G Benign/Likely benign ★★ 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-ser135tyr (accessed [today's date]).

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