Is NLGN3 p.Val204Phe (c.610G>T) pathogenic?

NLGN3 p.Val204Phe (c.610G>T) is classified Uncertain significance in NLGN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-16). AlphaMissense: ambiguous (0.4144); Absent from gnomAD v4.1.

How common is NLGN3 p.Val204Phe (c.610G>T) in the general population?

NLGN3 p.Val204Phe (c.610G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NLGN3 p.Val204Phe (c.610G>T)?

AlphaMissense predicts ambiguous (score 0.4144) — an in-silico prediction, not a clinical call.

NLGN3 p.Val204Phe

c.610G>T · rs2147880203 · VCV1702603

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4144 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4144	ambiguous
REVEL	0.634	indeterminate
SaProt	LLR -10.27	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.11	constrained · MANE · 89 bp · p 4.5e-06 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: NLGN3
Protein: p.Val204Phe
Coding: c.610G>T
MANE Select: NM_181303
dbSNP: rs2147880203
Type: single nucleotide variant
Location: chrX:71155246 (GRCh38)
Structure: AlphaFold pLDDT 76.80 · 1 PDB

Full NLGN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NLGN3 p.Val204Ala Pathogenic same residue
NLGN3 p.Arg748Gln Uncertain significance ★★ ⚠ same type
NLGN3 p.Arg785Cys Uncertain significance ★★ ⚠ same type
NLGN3 p.Arg785His Uncertain significance ★★ ⚠ same type
NLGN3 p.Arg847Gln Uncertain significance ★★ ⚠ same type
NLGN3 p.Asp492Asn Uncertain significance ★★ ⚠ same type
NLGN3 p.Leu31Phe Uncertain significance ★★ ⚠ same type
NLGN3 p.Leu477Phe 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/nlgn3-p-val204phe (accessed [today's date]).

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