Is RERE p.Phe1420Ser (c.4259T>C) pathogenic?

RERE p.Phe1420Ser (c.4259T>C) is classified Uncertain significance in RERE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-12). AlphaMissense: likely pathogenic (0.972); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with RERE p.Phe1420Ser (c.4259T>C)?

RERE p.Phe1420Ser (c.4259T>C) is associated with Inborn genetic diseases (ClinVar).

How common is RERE p.Phe1420Ser (c.4259T>C) in the general population?

RERE p.Phe1420Ser (c.4259T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RERE p.Phe1420Ser (c.4259T>C)?

AlphaMissense predicts likely pathogenic (score 0.972) — an in-silico prediction, not a clinical call.

RERE p.Phe1420Ser

c.4259T>C · rs2522692663 · VCV2260962

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.972 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.972	likely pathogenic
REVEL	0.482	indeterminate
SaProt	LLR -4.55	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 113 bp · p 0.13 · regional, not allelic
Overall
CADD	28.0	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.Phe1420Ser
Coding: c.4259T>C
MANE Select: NM_001042681
dbSNP: rs2522692663
Type: single nucleotide variant
Location: chr1:8358276 (GRCh38)
Gene constraint: LOEUF 0.459 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 54.51 · 1 PDB

Full RERE 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

RERE p.Phe1420Leu Uncertain significance ★ ⚠ same residue
RERE p.Gln858Ter Pathogenic/Likely pathogenic ★★ same condition
RERE p.Pro1424Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
RERE p.Ala617Val Uncertain significance ★★ ⚠ same condition
RERE p.Ala890Val Uncertain significance ★★ ⚠ same condition
RERE p.Arg1179Gln Uncertain significance ★★ ⚠ same condition
RERE p.Arg1179Leu Uncertain significance ★★ ⚠ same condition
RERE p.Arg1192Trp 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-phe1420ser (accessed [today's date]).

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