Is RNLS p.Asn232Ser (c.695A>G) pathogenic?

RNLS p.Asn232Ser (c.695A>G) is classified Likely benign in RNLS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-09). AlphaMissense: likely benign (0.0922); Rare (popmax 0.776%, mid).

How common is RNLS p.Asn232Ser (c.695A>G) in the general population?

RNLS p.Asn232Ser (c.695A>G) is rare (popmax 0.776%, mid) (gnomAD).

What do computational predictors say about RNLS p.Asn232Ser (c.695A>G)?

AlphaMissense predicts likely benign (score 0.0922) — an in-silico prediction, not a clinical call.

RNLS p.Asn232Ser

c.695A>G · rs117446494 · VCV2042254

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0922 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.776%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0922	likely benign
REVEL	0.331	indeterminate
SaProt	LLR -7.69	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 298 kb · p 0.87 · regional, not allelic
Overall
CADD	19.16	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 0.776% Middle Eastern · 47/6,054 alleles

Filtering AF 0.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.537%

Overall 0.37% 5,965/1,613,654 alleles · rare exomes 5,627/1,461,370 · genomes 338/152,284 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.776%	129
European (non-Finnish)	0.441%	227
Finnishnot grpmax-eligible	0.355%	282
Remaining individualsnot grpmax-eligible	0.29%	345
South Asian	0.247%	405
Admixed American	0.0634%	1,577
African / African-American	0.0613%	1,631
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,862
East Asian	0.00223%	44,878

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: RNLS
Protein: p.Asn232Ser
Coding: c.695A>G
MANE Select: NM_001031709
dbSNP: rs117446494
Type: single nucleotide variant
Location: chr10:88362557 (GRCh38)
Gene constraint: LOEUF 1.206 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.79 · 1 PDB

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

Similar variants

RNLS p.Asp102Glu Uncertain significance ★★ ⚠ same type
RNLS p.His307Leu Uncertain significance ★★ ⚠ same type
RNLS p.Ile226Thr Uncertain significance ★★ ⚠ same type
RNLS p.Leu335Pro Uncertain significance ★★ ⚠ same type
RNLS p.Pro249Leu Uncertain significance ★★ ⚠ same type
RNLS p.Ser217Gly Uncertain significance ★★ ⚠ same type
RNLS p.Thr160Pro Uncertain significance ★★ ⚠ same type
RNLS c.224+115A>G Benign ★★ 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/rnls-p-asn232ser (accessed [today's date]).

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