Is RELN p.Pro2510= (c.7530C>T) pathogenic?

RELN p.Pro2510= (c.7530C>T) is classified Benign in RELN (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-03). Common (popmax 14.4%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Norman-Roberts syndrome.

What condition is associated with RELN p.Pro2510= (c.7530C>T)?

RELN p.Pro2510= (c.7530C>T) is associated with Norman-Roberts syndrome, familial temporal lobe epilepsy 7 (ClinVar).

RELN p.Pro2510=

Q: How common is RELN p.Pro2510= (c.7530C>T) in the general population?

RELN p.Pro2510= (c.7530C>T) is common (popmax 14.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.7530C>T · rs2075038 · VCV130141

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 14.4%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

Norman-Roberts syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.9	GERP -4.2
Overall
CADD	0.121	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.4% South Asian · 13,101/91,040 alleles

Filtering AF 14.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.1%

Overall 4.2% 67,759/1,613,916 alleles · common exomes 61,968/1,461,790 · genomes 5,791/152,126 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	14.4%	7
Middle Eastern	6.69%	15
Admixed American	6.51%	15
Ashkenazi Jewishnot grpmax-eligible	6.23%	16
Remaining individualsnot grpmax-eligible	4.89%	20
East Asian	3.56%	28
European (non-Finnish)	3.39%	29
African / African-American	2.94%	34
Finnishnot grpmax-eligible	2.48%	40
Amishnot grpmax-eligible	2.3%	43

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: RELN
Protein: p.Pro2510=
Coding: c.7530C>T
MANE Select: NM_005045
dbSNP: rs2075038
Type: single nucleotide variant
Location: chr7:103522160 (GRCh38)
Gene constraint: LOEUF 0.276 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)

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

Disease context

Norman-Roberts syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial temporal lobe epilepsy 7

Similar variants

RELN c.3912+2T>G Likely pathogenic ★★ same condition
RELN c.7349+2T>C Likely pathogenic ★★ same condition
RELN p.Arg1622Ter Pathogenic/Likely pathogenic ★★ same condition
RELN c.1893-3C>T Uncertain significance ★★ same condition
RELN c.227-3C>T Uncertain significance ★★ same condition
RELN c.2465+5G>T Uncertain significance ★★ same condition
RELN c.6072+3A>G Uncertain significance ★★ same condition
RELN c.6072+4C>G 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/reln-p-pro2510 (accessed [today's date]).

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