Is RELN p.Phe736= (c.2208T>C) pathogenic?

RELN p.Phe736= (c.2208T>C) is classified Likely benign in RELN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-05). Absent from gnomAD v4.1; Associated with RELN-related disorder.

What condition is associated with RELN p.Phe736= (c.2208T>C)?

RELN p.Phe736= (c.2208T>C) is associated with RELN-related disorder (ClinVar).

How common is RELN p.Phe736= (c.2208T>C) in the general population?

RELN p.Phe736= (c.2208T>C) is absent from gnomAD v4.1 (gnomAD).

RELN p.Phe736=

c.2208T>C · rs2484802687 · VCV3038070

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

RELN-related disorder

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 3.1	GERP -0.68, phastCons 1
Overall
CADD	9.233	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RELN
Protein: p.Phe736=
Coding: c.2208T>C
MANE Select: NM_005045
dbSNP: rs2484802687
Type: single nucleotide variant
Location: chr7:103636330 (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

RELN-related disorder

Similar variants

RELN p.Phe736Cys Uncertain significance ★ same residue
RELN p.Arg3387Lys Uncertain significance ★★ same condition
RELN p.Gln9Ter Likely pathogenic ★ same condition
RELN p.Asp2646Glu Uncertain significance ★ ⚠ same condition
RELN p.Gln2460= Uncertain significance ★ same condition
RELN p.Gly269Glu Uncertain significance ★ same condition
RELN p.Ile982Thr Uncertain significance ★ same condition
RELN p.Met1996Val 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-phe736 (accessed [today's date]).

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