Is REN p.Ser247Arg (c.741C>A) pathogenic?

REN p.Ser247Arg (c.741C>A) is classified Uncertain significance in REN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely pathogenic (0.6475); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with REN p.Ser247Arg (c.741C>A)?

REN p.Ser247Arg (c.741C>A) is associated with Inborn genetic diseases (ClinVar).

How common is REN p.Ser247Arg (c.741C>A) in the general population?

REN p.Ser247Arg (c.741C>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about REN p.Ser247Arg (c.741C>A)?

AlphaMissense predicts likely pathogenic (score 0.6475) — an in-silico prediction, not a clinical call.

REN p.Ser247Arg

c.741C>A · rs1295851016 · VCV3152979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6475 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6475	likely pathogenic
REVEL	0.25	benign-leaning
SaProt	LLR -9.23	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.31 · evaluated, not missing
Pangolin	Δ0.20	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -6.7	GERP -3.7
Overall
CADD	2.494	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 0.000339% European (non-Finnish) · 4/1,179,808 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,668 alleles · very rare

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.Ser247Arg
Coding: c.741C>A
MANE Select: NM_001363642 · reported on NM_000537
dbSNP: rs1295851016
Type: single nucleotide variant
Location: chr1:204156754 (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

Similar variants

REN p.Ser247= Likely benign ★ same residue
REN p.Lys139Ter Pathogenic ★★ same condition
REN p.Arg119His Uncertain significance ★★ ⚠ same condition
REN p.Arg399His Uncertain significance ★★ ⚠ same condition
REN p.Gln160Arg Uncertain significance ★★ ⚠ same condition
REN p.Glu253Lys Uncertain significance ★★ ⚠ same condition
REN p.Glu310Lys Uncertain significance ★★ ⚠ same condition
REN p.Glu89Lys 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-ser247arg (accessed [today's date]).

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