Is SMO p.Pro60= (c.180G>T) pathogenic?

SMO p.Pro60= (c.180G>T) is classified Likely benign in SMO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-15). Very rare (popmax 0.00106%, nfe).

How common is SMO p.Pro60= (c.180G>T) in the general population?

SMO p.Pro60= (c.180G>T) is very rare (popmax 0.00106%, nfe) (gnomAD).

SMO p.Pro60=

c.180G>T · VCV4897941

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00106%, nfe)

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 4.8	GERP 1.2, phastCons 1
Overall
CADD	12.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00106% European (non-Finnish) · 12/1,137,260 alleles

Filtering AF 0.000563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000444%

Overall 0.00086% 13/1,512,206 alleles · very rare exomes 13/1,360,042 · genomes 0/152,164 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0017%	58,846
European (non-Finnish)grpmax	0.00106%	94,771

Remaining individuals 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: SMO
Protein: p.Pro60=
Coding: c.180G>T
MANE Select: NM_005631
Type: single nucleotide variant
Location: chr7:129189331 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.55 · 15 PDB
Residue 60: the 'disordered' region; an α-helix

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

Similar variants

SMO p.Leu412Phe Pathogenic ★★ ⚠ same type
SMO p.Arg512Cys Uncertain significance ★★ ⚠ same type
SMO p.Arg709Gln Uncertain significance ★★ ⚠ same type
SMO p.Asp201Val Uncertain significance ★★ ⚠ same type
SMO p.Gly598Val Uncertain significance ★★ ⚠ same type
SMO p.Leu197= Uncertain significance ★★ same type
SMO p.Val129Ile Uncertain significance ★★ ⚠ same type
SMO p.Val195Met 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/smo-p-pro60 (accessed [today's date]).

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