Is SOST p.Arg160Pro (c.479G>C) pathogenic?

SOST p.Arg160Pro (c.479G>C) is classified Uncertain significance in SOST (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-17). AlphaMissense: likely benign (0.3395); Ultra-rare (popmax 0.0109%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SOST p.Arg160Pro (c.479G>C)?

SOST p.Arg160Pro (c.479G>C) is associated with Inborn genetic diseases (ClinVar).

How common is SOST p.Arg160Pro (c.479G>C) in the general population?

SOST p.Arg160Pro (c.479G>C) is ultra-rare (popmax 0.0109%, nfe) (gnomAD).

What do computational predictors say about SOST p.Arg160Pro (c.479G>C)?

AlphaMissense predicts likely benign (score 0.3395) — an in-silico prediction, not a clinical call.

SOST p.Arg160Pro

c.479G>C · rs199579218 · VCV2520855

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3395 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3395	likely benign
REVEL	0.651	pathogenic-leaning
SaProt	LLR -10.43	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.24, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,396 bp · p 0.26 · regional, not allelic
Overall
CADD	28.4	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 0.0109% European (non-Finnish) · 129/1,178,126 alleles

Filtering AF 0.00937% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00881%

Overall 0.00858% 137/1,596,384 alleles · ultra-rare exomes 128/1,444,190 · genomes 9/152,194 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0109%	9,133
Remaining individualsnot grpmax-eligible	0.00965%	10,364
Admixed American	0.00167%	59,746
African / African-American	0.00136%	73,752

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: SOST
Protein: p.Arg160Pro
Coding: c.479G>C
MANE Select: NM_025237
dbSNP: rs199579218
Type: single nucleotide variant
Location: chr17:43755505 (GRCh38)
Gene constraint: LOEUF 1.634 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.73 · 3 PDB
Residue 160: the ctck domain; a β-strand

Full SOST 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

SOST p.Asn117Ser Uncertain significance ★★ ⚠ same condition
SOST p.Gly62Arg Uncertain significance ★★ ⚠ same condition
SOST p.Ala199Ser Uncertain significance ★ ⚠ same condition
SOST p.Ala6Val Uncertain significance ★ ⚠ same condition
SOST p.Arg126Pro Uncertain significance ★ ⚠ same condition
SOST p.Arg188Trp Uncertain significance ★ ⚠ same condition
SOST p.Arg64Trp Uncertain significance ★ ⚠ same condition
SOST p.Gln24Leu 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/sost-p-arg160pro (accessed [today's date]).

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