Is SKI p.Phe24= (c.72C>T) pathogenic?

SKI p.Phe24= (c.72C>T) is classified Likely benign in SKI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). Very rare (popmax 0.0015%, afr); Associated with Shprintzen-Goldberg syndrome.

What condition is associated with SKI p.Phe24= (c.72C>T)?

SKI p.Phe24= (c.72C>T) is associated with Shprintzen-Goldberg syndrome (ClinVar).

How common is SKI p.Phe24= (c.72C>T) in the general population?

SKI p.Phe24= (c.72C>T) is very rare (popmax 0.0015%, afr) (gnomAD).

SKI p.Phe24=

c.72C>T · rs953342598 · VCV1547206

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0015%, afr)

Conditions

Shprintzen-Goldberg syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.3	GERP -0.043, phastCons 1
Overall
CADD	14.48	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0015% African / African-American · 1/66,816 alleles

Filtering AF 3.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000213% 3/1,406,618 alleles · very rare exomes 2/1,257,156 · genomes 1/149,462 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0015%	66,816
European (non-Finnish)	0.000186%	536,904

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: SKI
Protein: p.Phe24=
Coding: c.72C>T
MANE Select: NM_003036
dbSNP: rs953342598
Type: single nucleotide variant
Location: chr1:2228838 (GRCh38)
Gene constraint: LOEUF 0.809 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.18 · 4 PDB
Residue 24: an α-helix

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

Disease context

Shprintzen-Goldberg syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SKI p.Phe24Ser Uncertain significance ★ ⚠ same residue
SKI p.Gly116Glu Pathogenic/Likely pathogenic ★★ same condition
SKI p.Gly117Arg Pathogenic/Likely pathogenic ★★ same condition
SKI p.Gly117Ser Pathogenic/Likely pathogenic ★★ same condition
SKI p.Gly34Cys Pathogenic ★★ ⚠ same condition
SKI p.Gly34Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
SKI p.Gly34Val Pathogenic ★★ ⚠ same condition
SKI p.Leu32Val Pathogenic ★★ ⚠ 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/ski-p-phe24 (accessed [today's date]).

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