Is SGTA p.Pro72= (c.216G>A) pathogenic?

SGTA p.Pro72= (c.216G>A) is classified Benign in SGTA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-14). Common (popmax 5.01%, afr) — too common for a highly-penetrant pathogenic allele.

SGTA p.Pro72=

Q: How common is SGTA p.Pro72= (c.216G>A) in the general population?

SGTA p.Pro72= (c.216G>A) is common (popmax 5.01%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.216G>A · rs77882038 · VCV713387

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.01%, afr) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -3.5
Overall
CADD	0.268	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.01% African / African-American · 3,750/74,920 alleles

Filtering AF 4.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.82%

Overall 0.272% 4,377/1,609,696 alleles · common exomes 2,162/1,457,474 · genomes 2,215/152,222 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.01%	20
Remaining individualsnot grpmax-eligible	0.408%	245
Admixed American	0.37%	270
Middle Eastern	0.0884%	1,131
South Asian	0.0155%	6,447
European (non-Finnish)	0.0109%	9,135
Finnishnot grpmax-eligible	0.00631%	15,838

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: SGTA
Protein: p.Pro72=
Coding: c.216G>A
MANE Select: NM_003021
dbSNP: rs77882038
Type: single nucleotide variant
Location: chr19:2767212 (GRCh38)
Gene constraint: LOEUF 0.747 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.86 · 5 PDB
Residue 72: the 'disordered' region

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

Similar variants

SGTA p.Ser235= Benign ★★ same type
SGTA p.Ala10Thr Uncertain significance ★ ⚠ same type
SGTA p.Ala42Val Uncertain significance ★ ⚠ same type
SGTA p.Ala53Gly Uncertain significance ★ ⚠ same type
SGTA p.Ala66Thr Uncertain significance ★ ⚠ same type
SGTA p.Ala66Val Uncertain significance ★ ⚠ same type
SGTA p.Arg302Pro Uncertain significance ★ ⚠ same type
SGTA p.Gln275Ter 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/sgta-p-pro72 (accessed [today's date]).

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