Is RELN p.Pro2629= (c.7887T>C) pathogenic?

RELN p.Pro2629= (c.7887T>C) is classified Benign in RELN (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-03). Common (popmax 28.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Norman-Roberts syndrome.

What condition is associated with RELN p.Pro2629= (c.7887T>C)?

RELN p.Pro2629= (c.7887T>C) is associated with Norman-Roberts syndrome, familial temporal lobe epilepsy 7 (ClinVar).

RELN p.Pro2629=

Q: How common is RELN p.Pro2629= (c.7887T>C) in the general population?

RELN p.Pro2629= (c.7887T>C) is common (popmax 28.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.7887T>C · rs56345626 · VCV130142

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 28.7%, eas) — 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	all four deltas below 0.2 · A>T here scores Δ0.99 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.11	GERP -2, phastCons 0.005
Overall
CADD	7.661	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 28.7% East Asian · 12,878/44,856 alleles

Filtering AF 28.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 28.1%

Overall 18.2% 294,272/1,613,810 alleles · common exomes 268,037/1,461,682 · genomes 26,235/152,128 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	28.7%	3
Finnishnot grpmax-eligible	21.1%	5
Middle Eastern	19.9%	5
Remaining individualsnot grpmax-eligible	18.4%	5
European (non-Finnish)	18.4%	5
Amishnot grpmax-eligible	18.1%	6
Ashkenazi Jewishnot grpmax-eligible	17%	6
South Asian	15.9%	6
Admixed American	15%	7
African / African-American	13.1%	8

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.Pro2629=
Coding: c.7887T>C
MANE Select: NM_005045
dbSNP: rs56345626
Type: single nucleotide variant
Location: chr7:103515417 (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 p.Pro2629Arg Uncertain significance ★ ⚠ same residue
RELN p.Pro2629Leu Uncertain significance ★ ⚠ same residue
RELN p.Pro2629Ala Likely benign ★ same residue
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

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-pro2629 (accessed [today's date]).

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