Is RERE p.Ser712Pro (c.2134T>C) pathogenic?

RERE p.Ser712Pro (c.2134T>C) is classified Uncertain significance in RERE (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-27). AlphaMissense: likely pathogenic (0.9135); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with or without anomalies of the brain, eye, or heart.

What condition is associated with RERE p.Ser712Pro (c.2134T>C)?

RERE p.Ser712Pro (c.2134T>C) is associated with neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (ClinVar).

How common is RERE p.Ser712Pro (c.2134T>C) in the general population?

RERE p.Ser712Pro (c.2134T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RERE p.Ser712Pro (c.2134T>C)?

AlphaMissense predicts likely pathogenic (score 0.9135) — an in-silico prediction, not a clinical call.

RERE p.Ser712Pro

c.2134T>C · rs1570039432 · VCV638397

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9135 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neurodevelopmental disorder with or without anomalies of the brain, eye, or heart

Computational evidence

Protein change
AlphaMissense	0.9135	likely pathogenic
REVEL	0.457	indeterminate
SaProt	LLR -8.86	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 5,731 bp · p 0.0029 · regional, not allelic
Overall
CADD	28.1	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: RERE
Protein: p.Ser712Pro
Coding: c.2134T>C
MANE Select: NM_001042681
dbSNP: rs1570039432
Type: single nucleotide variant
Location: chr1:8361373 (GRCh38)
Gene constraint: LOEUF 0.459 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 54.51 · 1 PDB
Residue 712: the 'disordered' region

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

Disease context

neurodevelopmental disorder with or without anomalies of the brain, eye, or heart — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RERE p.His1429Arg Likely pathogenic ★★ same condition
RERE p.His1431Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
RERE p.His1433Pro Likely pathogenic ★★ ⚠ same condition
RERE p.His1435Arg Pathogenic/Likely pathogenic ★★ same condition
RERE p.His1435Leu Likely pathogenic ★★ same condition
RERE p.Pro1049Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
RERE p.Pro1424Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
RERE p.Ala1506Thr 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/rere-p-ser712pro (accessed [today's date]).

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