Is NTNG2 p.Pro116= (c.348C>G) pathogenic?

NTNG2 p.Pro116= (c.348C>G) is classified Likely benign in NTNG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). Ultra-rare (popmax 0.0615%, sas).

How common is NTNG2 p.Pro116= (c.348C>G) in the general population?

NTNG2 p.Pro116= (c.348C>G) is ultra-rare (popmax 0.0615%, sas) (gnomAD).

NTNG2 p.Pro116=

c.348C>G · rs758834216 · VCV2659641

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0615%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.6	GERP -5.6
Overall
CADD	2.998	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0615% South Asian · 56/91,088 alleles

Filtering AF 0.0486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.044%

Overall 0.00514% 83/1,613,930 alleles · ultra-rare exomes 77/1,461,578 · genomes 6/152,352 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0615%	1,627
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0128%	7,813
European (non-Finnish)	0.00153%	65,557

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: NTNG2
Protein: p.Pro116=
Coding: c.348C>G
MANE Select: NM_032536
dbSNP: rs758834216
Type: single nucleotide variant
Location: chr9:132198100 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 85.03 · 3 PDB
Residue 116: the laminin n-terminal domain; a turn

Full NTNG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NTNG2 p.Arg183Gly Uncertain significance ★★ ⚠ same type
NTNG2 p.Gly317Ser Uncertain significance ★★ ⚠ same type
NTNG1 c.1087+10829A>G Benign ★★ same type
NTNG1 c.1087+10866G>A Benign ★★ same type
NTNG1 c.887+97C>T Benign ★★ same type
NTNG1 c.-120G>C Benign ★★ same type
NTNG1 c.-293A>G Benign ★★ same type
NTNG1 c.*127A>C 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/ntng2-p-pro116 (accessed [today's date]).

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