Is PSD p.Ala650= (c.1950C>T) pathogenic?

PSD p.Ala650= (c.1950C>T) is classified Likely benign in PSD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-16). Rare (popmax 0.156%, afr).

How common is PSD p.Ala650= (c.1950C>T) in the general population?

PSD p.Ala650= (c.1950C>T) is rare (popmax 0.156%, afr) (gnomAD).

PSD p.Ala650=

c.1950C>T · rs35284232 · VCV739565

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.156%, 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 -0.55	GERP -4, phastCons 0.004
Overall
CADD	9.758	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.156% African / African-American · 117/74,930 alleles

Filtering AF 0.133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.00752% 121/1,608,896 alleles · rare exomes 60/1,456,684 · genomes 61/152,212 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.156%	640
Middle Eastern	0.0165%	6,046
Remaining individualsnot grpmax-eligible	0.00322%	31,102
European (non-Finnish)	8.5e-05%	1,176,143

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.Ala650=
Coding: c.1950C>T
MANE Select: NM_002779
dbSNP: rs35284232
Type: single nucleotide variant
Location: chr10:102411109 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 56.76
Residue 650: 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-ala650 (accessed [today's date]).

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