Is GSC p.Pro36= (c.108G>A) pathogenic?

GSC p.Pro36= (c.108G>A) is classified Benign in GSC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Low-frequency (popmax 3.09%, mid); Associated with short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome.

How common is GSC p.Pro36= (c.108G>A) in the general population?

GSC p.Pro36= (c.108G>A) is low-frequency (popmax 3.09%, mid) (gnomAD).

GSC p.Pro36=

Q: What condition is associated with GSC p.Pro36= (c.108G>A)?

GSC p.Pro36= (c.108G>A) is associated with short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome (ClinVar).

c.108G>A · rs191352872 · VCV1285309

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.09%, mid)

Conditions

short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome

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 0.99	GERP 0.33, phastCons 1
Overall
CADD	15.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.09% Middle Eastern · 163/5,282 alleles

Filtering AF 2.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.86%

Overall 1.16% 17,762/1,530,476 alleles · low-frequency exomes 15,350/1,378,228 · genomes 2,412/152,248 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	3.09%	32
African / African-American	3.01%	33
Remaining individualsnot grpmax-eligible	1.42%	71
Ashkenazi Jewishnot grpmax-eligible	1.36%	74
European (non-Finnish)	1.15%	87
Admixed American	1.02%	98
Finnishnot grpmax-eligible	0.508%	197
South Asian	0.371%	270
East Asian	0.0125%	7,988

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: GSC
Protein: p.Pro36=
Coding: c.108G>A
MANE Select: NM_173849
dbSNP: rs191352872
Type: single nucleotide variant
Location: chr14:94769908 (GRCh38)
Gene constraint: LOEUF 1.398 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.68 · 1 PDB

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

Disease context

short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GSC p.Gly86Arg Uncertain significance ★ ⚠ same condition
GSC c.355+1G>C Pathogenic same condition
GSC p.Gln134Ter Pathogenic same condition
GSC p.Gly66fs Pathogenic same condition
GSC p.Ala26Val Uncertain significance ★★ ⚠ same type
GSC p.Ala30Val Uncertain significance ★★ ⚠ same type
GSC p.Lys183Gln Uncertain significance ★★ ⚠ same type
GSC p.Tyr54Ser 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/gsc-p-pro36 (accessed [today's date]).

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