Is RTN4IP1 p.Phe342Val (c.1024T>G) pathogenic?

RTN4IP1 p.Phe342Val (c.1024T>G) is classified Uncertain significance in RTN4IP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-30). AlphaMissense: ambiguous (0.4961); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RTN4IP1 p.Phe342Val (c.1024T>G)?

RTN4IP1 p.Phe342Val (c.1024T>G) is associated with Inborn genetic diseases (ClinVar).

How common is RTN4IP1 p.Phe342Val (c.1024T>G) in the general population?

RTN4IP1 p.Phe342Val (c.1024T>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about RTN4IP1 p.Phe342Val (c.1024T>G)?

AlphaMissense predicts ambiguous (score 0.4961) — an in-silico prediction, not a clinical call.

RTN4IP1 p.Phe342Val

c.1024T>G · rs760197663 · VCV1486522

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4961 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4961	ambiguous
REVEL	0.594	indeterminate
SaProt	LLR -8.07	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 57 kb · p 0.005 · regional, not allelic
Overall
CADD	26.6	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

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,714 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,692 alleles · very rare exomes 4/1,461,316 · genomes 0/152,376 · joint denominator

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: RTN4IP1
Protein: p.Phe342Val
Coding: c.1024T>G
MANE Select: NM_032730
dbSNP: rs760197663
Type: single nucleotide variant
Location: chr6:106583387 (GRCh38)
Gene constraint: LOEUF 0.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.54 · 1 PDB
Residue 342: the enoyl reductase (er) domain; a UniProt-annotated variant site (in opa10)

Full RTN4IP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RTN4IP1 c.496-3T>C Uncertain significance ★★ same condition
RTN4IP1 p.Ala230Gly Uncertain significance ★★ ⚠ same condition
RTN4IP1 p.Ala249Thr Uncertain significance ★★ same condition
RTN4IP1 p.Ala345Pro Uncertain significance ★★ ⚠ same condition
RTN4IP1 p.Ala80Gly Uncertain significance ★★ ⚠ same condition
RTN4IP1 p.Arg10Lys Uncertain significance ★★ ⚠ same condition
RTN4IP1 p.Asp133Glu Uncertain significance ★★ ⚠ same condition
RTN4IP1 p.Asp229Tyr 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/rtn4ip1-p-phe342val (accessed [today's date]).

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