Is PSD p.Arg7Cys (c.19C>T) pathogenic?

PSD p.Arg7Cys (c.19C>T) is classified Uncertain significance in PSD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely pathogenic (0.6935); Very rare (popmax 0.00463%, eas).

How common is PSD p.Arg7Cys (c.19C>T) in the general population?

PSD p.Arg7Cys (c.19C>T) is very rare (popmax 0.00463%, eas) (gnomAD).

What do computational predictors say about PSD p.Arg7Cys (c.19C>T)?

AlphaMissense predicts likely pathogenic (score 0.6935) — an in-silico prediction, not a clinical call.

PSD p.Arg7Cys

c.19C>T · rs1219096955 · VCV3220132

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6935 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00463%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6935	likely pathogenic
REVEL	0.154	moderately benign-leaning
SaProt	LLR -7.49	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 4,529 bp · p 0.00029 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00463% East Asian · 2/43,206 alleles

Filtering AF 0.000767% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000287%

Overall 0.000762% 12/1,575,548 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00463%	21,603
Admixed American	0.00179%	55,726
African / African-American	0.00135%	73,926
South Asian	0.00112%	88,978
European (non-Finnish)	0.000599%	167,041

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.Arg7Cys
Coding: c.19C>T
MANE Select: NM_002779
dbSNP: rs1219096955
Type: single nucleotide variant
Location: chr10:102417020 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 56.76

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-arg7cys (accessed [today's date]).

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