Is PGD p.Thr245= (c.735C>T) pathogenic?

PGD p.Thr245= (c.735C>T) is classified Benign in PGD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-23). Low-frequency (popmax 1.15%, afr).

How common is PGD p.Thr245= (c.735C>T) in the general population?

PGD p.Thr245= (c.735C>T) is low-frequency (popmax 1.15%, afr) (gnomAD).

PGD p.Thr245=

c.735C>T · rs79502417 · VCV716657

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, afr)

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 -7.1	GERP -3.7
Overall
CADD	1.166	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.15% African / African-American · 859/75,008 alleles

Filtering AF 1.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.06%

Overall 0.0607% 980/1,614,054 alleles · low-frequency exomes 491/1,461,778 · genomes 489/152,276 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.15%	87
Remaining individualsnot grpmax-eligible	0.0672%	1,488
Middle Eastern	0.066%	1,516
Admixed American	0.0566%	1,765
South Asian	0.011%	9,108
European (non-Finnish)	0.00263%	38,063

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: PGD
Protein: p.Thr245=
Coding: c.735C>T
MANE Select: NM_002631
dbSNP: rs79502417
Type: single nucleotide variant
Location: chr1:10413142 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 96.98 · 4 PDB

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

Similar variants

PGD p.Thr245Asn Uncertain significance ★ ⚠ same residue
PGD c.519+2C>T Uncertain significance ★ same type
PGD p.Ala149Gly Uncertain significance ★ ⚠ same type
PGD p.Ala258Val Uncertain significance ★ ⚠ same type
PGD p.Ala336Pro Uncertain significance ★ ⚠ same type
PGD p.Ala345Gly Uncertain significance ★ ⚠ same type
PGD p.Arg407Gln Uncertain significance ★ ⚠ same type
PGD p.Asn354Ser 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/pgd-p-thr245 (accessed [today's date]).

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