Is RERE p.Val233Phe (c.697G>T) pathogenic?

RERE p.Val233Phe (c.697G>T) is classified Uncertain significance in RERE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely pathogenic (0.9397); Very rare (popmax 0.00051%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RERE p.Val233Phe (c.697G>T)?

RERE p.Val233Phe (c.697G>T) is associated with Inborn genetic diseases (ClinVar).

How common is RERE p.Val233Phe (c.697G>T) in the general population?

RERE p.Val233Phe (c.697G>T) is very rare (popmax 0.00051%, nfe) (gnomAD).

What do computational predictors say about RERE p.Val233Phe (c.697G>T)?

AlphaMissense predicts likely pathogenic (score 0.9397) — an in-silico prediction, not a clinical call.

RERE p.Val233Phe

c.697G>T · rs147116390 · VCV2260963

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9397 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00051%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9397	likely pathogenic
REVEL	0.656	pathogenic-leaning
SaProt	LLR -6.95	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 15 kb · p 0.16 · regional, not allelic
Overall
CADD	23.9	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 0.00051% European (non-Finnish) · 6/1,175,758 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000373% 6/1,609,364 alleles · very rare exomes 6/1,457,080 · genomes 0/152,284 · joint denominator

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: RERE
Protein: p.Val233Phe
Coding: c.697G>T
MANE Select: NM_001042681
dbSNP: rs147116390
Type: single nucleotide variant
Location: chr1:8556503 (GRCh38)
Gene constraint: LOEUF 0.459 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 54.51 · 1 PDB
Residue 233: the bah domain

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.Val233Ile Conflicting classifications of pathogenicity ★ ⚠ 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-val233phe (accessed [today's date]).

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