Is RELN p.Phe1963Leu (c.5889T>G) pathogenic?

RELN p.Phe1963Leu (c.5889T>G) is classified Uncertain significance in RELN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-11). AlphaMissense: likely pathogenic (0.566); No allele count reported in gnomAD v4.1 (AN 1,613,996).

How common is RELN p.Phe1963Leu (c.5889T>G) in the general population?

RELN p.Phe1963Leu (c.5889T>G) is no allele count reported in gnomAD v4.1 (AN 1,613,996) (gnomAD).

What do computational predictors say about RELN p.Phe1963Leu (c.5889T>G)?

AlphaMissense predicts likely pathogenic (score 0.566) — an in-silico prediction, not a clinical call.

RELN p.Phe1963Leu

c.5889T>G · VCV4897333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.566 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,996)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.566	likely pathogenic
REVEL	0.067	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.6	GERP -0.42, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 67 kb · p 2.1e-16 · regional, not allelic
Overall
CADD	14.24	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,996). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RELN
Protein: p.Phe1963Leu
Coding: c.5889T>G
MANE Select: NM_005045
Type: single nucleotide variant
Location: chr7:103553740 (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

Similar variants

RELN p.Phe1963= Likely benign ★ same residue
RELN c.3912+2T>G Likely pathogenic ★★ same type
RELN c.7349+2T>C Likely pathogenic ★★ same type
RELN p.Arg1622Ter Pathogenic/Likely pathogenic ★★ same type
RELN c.1893-3C>T Uncertain significance ★★ same type
RELN c.227-3C>T Uncertain significance ★★ same type
RELN c.2465+5G>T Uncertain significance ★★ same type
RELN c.6072+3A>G Uncertain significance ★★ same type

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-phe1963leu (accessed [today's date]).

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