Is RERE p.Arg508= (c.1524C>T) pathogenic?

RERE p.Arg508= (c.1524C>T) is classified Benign/Likely benign in RERE (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-18). Low-frequency (popmax 1.15%, afr); Associated with neurodevelopmental disorder with or without anomalies of the brain, eye, or heart.

How common is RERE p.Arg508= (c.1524C>T) in the general population?

RERE p.Arg508= (c.1524C>T) is low-frequency (popmax 1.15%, afr) (gnomAD).

RERE p.Arg508=

Q: What condition is associated with RERE p.Arg508= (c.1524C>T)?

RERE p.Arg508= (c.1524C>T) is associated with neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (ClinVar).

c.1524C>T · rs139299521 · VCV1599655

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, afr)

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1.2, phastCons 1
Overall
CADD	9.78	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.15% African / African-American · 861/75,010 alleles

Filtering AF 1.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.06%

Overall 0.0571% 921/1,613,804 alleles · low-frequency exomes 438/1,461,546 · genomes 483/152,258 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.15%	87
Remaining individualsnot grpmax-eligible	0.0592%	1,688
Admixed American	0.0267%	3,751
Middle Eastern	0.0165%	6,060
South Asian	0.0022%	45,536
European (non-Finnish)	0.000339%	294,958

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.Arg508=
Coding: c.1524C>T
MANE Select: NM_001042681
dbSNP: rs139299521
Type: single nucleotide variant
Location: chr1:8364762 (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

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.Arg508Leu Uncertain significance ★ ⚠ same residue
RERE p.Arg508His Uncertain significance ★ ⚠ same residue
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

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-arg508 (accessed [today's date]).

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