Is RTN3 p.Ser10= (c.30C>T) pathogenic?

RTN3 p.Ser10= (c.30C>T) is classified Benign in RTN3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-11). Low-frequency (popmax 1.11%, nfe).

How common is RTN3 p.Ser10= (c.30C>T) in the general population?

RTN3 p.Ser10= (c.30C>T) is low-frequency (popmax 1.11%, nfe) (gnomAD).

RTN3 p.Ser10=

c.30C>T · rs11551949 · VCV777228

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.11%, nfe)

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 0.36	GERP -3.1, phastCons 0.99
Overall
CADD	11.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.11% European (non-Finnish) · 13,141/1,178,628 alleles

Filtering AF 1.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.09%

Overall 0.953% 15,355/1,611,502 alleles · low-frequency exomes 14,176/1,459,114 · genomes 1,179/152,388 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.28%	44
European (non-Finnish)grpmax	1.11%	90
Remaining individualsnot grpmax-eligible	0.904%	111
Admixed American	0.632%	158
Finnishnot grpmax-eligible	0.606%	165
Middle Eastern	0.215%	464
African / African-American	0.186%	539
Amishnot grpmax-eligible	0.11%	912
South Asian	0.066%	1,514
East Asian	0.00224%	44,728

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: RTN3
Protein: p.Ser10=
Coding: c.30C>T
MANE Select: NM_001265589
dbSNP: rs11551949
Type: single nucleotide variant
Location: chr11:63681666 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.42 · 1 PDB
Residue 10: the 'disordered' region

Full RTN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RTN3 p.Ala198Thr Uncertain significance ★ ⚠ same type
RTN3 p.Ala256Thr Uncertain significance ★ ⚠ same type
RTN3 p.Ala2Val Uncertain significance ★ ⚠ same type
RTN3 p.Ala321Val Uncertain significance ★ ⚠ same type
RTN3 p.Ala448Gly Uncertain significance ★ ⚠ same type
RTN3 p.Ala510Pro Uncertain significance ★ ⚠ same type
RTN3 p.Ala657Val Uncertain significance ★ ⚠ same type
RTN3 p.Ala676Val 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/rtn3-p-ser10 (accessed [today's date]).

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