Is RELN p.Pro2875= (c.8625G>A) pathogenic?

RELN p.Pro2875= (c.8625G>A) is classified Likely benign in RELN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-29). Rare (popmax 0.16%, eas); Associated with familial temporal lobe epilepsy 7.

What condition is associated with RELN p.Pro2875= (c.8625G>A)?

RELN p.Pro2875= (c.8625G>A) is associated with familial temporal lobe epilepsy 7, Norman-Roberts syndrome (ClinVar).

How common is RELN p.Pro2875= (c.8625G>A) in the general population?

RELN p.Pro2875= (c.8625G>A) is rare (popmax 0.16%, eas) (gnomAD).

RELN p.Pro2875=

c.8625G>A · rs190273964 · VCV512370

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.16%, eas)

Conditions

familial temporal lobe epilepsy 7

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -14	GERP -3.6
Overall
CADD	1.542	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.16% East Asian · 72/44,884 alleles

Filtering AF 0.131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.12%

Overall 0.00545% 88/1,614,072 alleles · rare exomes 76/1,461,830 · genomes 12/152,242 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.16%	623
Admixed American	0.00667%	15,002
African / African-American	0.00533%	18,758
Remaining individualsnot grpmax-eligible	0.0016%	62,504
South Asian	0.0011%	91,070
European (non-Finnish)	0.000508%	196,663

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.Pro2875=
Coding: c.8625G>A
MANE Select: NM_005045
dbSNP: rs190273964
Type: single nucleotide variant
Location: chr7:103500787 (GRCh38)

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

Disease context

familial temporal lobe epilepsy 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Norman-Roberts syndrome

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-pro2875 (accessed [today's date]).

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