Is PSD p.Gly680= (c.2040G>A) pathogenic?

PSD p.Gly680= (c.2040G>A) is classified Likely benign in PSD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-26). Very rare (popmax 0.00133%, afr).

How common is PSD p.Gly680= (c.2040G>A) in the general population?

PSD p.Gly680= (c.2040G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

PSD p.Gly680=

c.2040G>A · rs1302761895 · VCV746061

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.32	GERP -4.3, phastCons 0.98
Overall
CADD	11.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,912 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,613,876 alleles · very rare exomes 5/1,461,722 · genomes 3/152,154 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,912
European (non-Finnish)	0.000593%	168,560

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: PSD
Protein: p.Gly680=
Coding: c.2040G>A
MANE Select: NM_002779
dbSNP: rs1302761895
Type: single nucleotide variant
Location: chr10:102410909 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 56.76
Residue 680: the sec7 domain

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

Similar variants

PSD p.Gly336Ser Benign ★★ same type
PSD p.Leu659= Benign ★★ same type
PSD p.Ala1017Pro Uncertain significance ★ ⚠ same type
PSD p.Ala185Pro Uncertain significance ★ ⚠ same type
PSD p.Ala204Val Uncertain significance ★ ⚠ same type
PSD p.Ala260Val Uncertain significance ★ ⚠ same type
PSD p.Ala311Asp Uncertain significance ★ ⚠ same type
PSD p.Ala457Thr 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/psd-p-gly680 (accessed [today's date]).

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