Is RELN p.Asp207= (c.621C>T) pathogenic?

RELN p.Asp207= (c.621C>T) is classified Benign in RELN (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.79%, afr); Associated with Norman-Roberts syndrome.

What condition is associated with RELN p.Asp207= (c.621C>T)?

RELN p.Asp207= (c.621C>T) is associated with Norman-Roberts syndrome, familial temporal lobe epilepsy 7 (ClinVar).

How common is RELN p.Asp207= (c.621C>T) in the general population?

RELN p.Asp207= (c.621C>T) is low-frequency (popmax 1.79%, afr) (gnomAD).

RELN p.Asp207=

c.621C>T · rs114627891 · VCV358417

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.79%, afr)

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 3.9	GERP 0.69, phastCons 1
Overall
CADD	7.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.79% African / African-American · 1,340/74,978 alleles

Filtering AF 1.71% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.68%

Overall 0.0913% 1,473/1,613,168 alleles · low-frequency exomes 682/1,460,900 · genomes 791/152,268 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.79%	56
Remaining individualsnot grpmax-eligible	0.109%	919
Admixed American	0.095%	1,053
South Asian	0.0022%	45,536
European (non-Finnish)	0.000509%	196,539

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.Asp207=
Coding: c.621C>T
MANE Select: NM_005045
dbSNP: rs114627891
Type: single nucleotide variant
Location: chr7:103749461 (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-asp207 (accessed [today's date]).

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