Is PSD p.Arg23His (c.68G>A) pathogenic?

PSD p.Arg23His (c.68G>A) is classified Uncertain significance in PSD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). AlphaMissense: ambiguous (0.367); Very rare (popmax 0.0033%, sas).

How common is PSD p.Arg23His (c.68G>A) in the general population?

PSD p.Arg23His (c.68G>A) is very rare (popmax 0.0033%, sas) (gnomAD).

What do computational predictors say about PSD p.Arg23His (c.68G>A)?

AlphaMissense predicts ambiguous (score 0.367) — an in-silico prediction, not a clinical call.

PSD p.Arg23His

c.68G>A · VCV3310825

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.367 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.367	ambiguous
REVEL	0.066	moderately benign-leaning
SaProt	LLR -7.71	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 0.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 4,529 bp · p 0.00029 · regional, not allelic
Overall
CADD	29.7	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 0.0033% South Asian · 3/90,904 alleles

Filtering AF 0.000877% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.0005% 8/1,599,362 alleles · very rare exomes 8/1,447,934 · genomes 0/151,428 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,301
European (non-Finnish)	0.000424%	235,819

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.Arg23His
Coding: c.68G>A
MANE Select: NM_002779
Type: single nucleotide variant
Location: chr10:102416971 (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-arg23his (accessed [today's date]).

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