Is PSD p.Arg202His (c.605G>A) pathogenic?

PSD p.Arg202His (c.605G>A) is classified Likely benign in PSD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.0567); Rare (popmax 0.248%, sas).

How common is PSD p.Arg202His (c.605G>A) in the general population?

PSD p.Arg202His (c.605G>A) is rare (popmax 0.248%, sas) (gnomAD).

What do computational predictors say about PSD p.Arg202His (c.605G>A)?

AlphaMissense predicts likely benign (score 0.0567) — an in-silico prediction, not a clinical call.

PSD p.Arg202His

c.605G>A · VCV4146088

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0567 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.248%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0567	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -7.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.92	GERP -3.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 4,529 bp · p 0.00029 · regional, not allelic
Overall
CADD	11.03	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 0.248% South Asian · 224/90,500 alleles

Filtering AF 0.221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.211%

Overall 0.0436% 703/1,611,296 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.987%	101
Ashkenazi Jewishnot grpmax-eligible	0.377%	265
South Asiangrpmax	0.248%	404
Middle Eastern	0.0991%	1,009
Admixed American	0.0588%	1,700
Remaining individualsnot grpmax-eligible	0.0529%	1,890
European (non-Finnish)	0.0229%	4,366
African / African-American	0.012%	8,334
East Asian	0.00893%	11,201
Finnishnot grpmax-eligible	0.00314%	31,862

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg202His
Coding: c.605G>A
MANE Select: NM_002779
Type: single nucleotide variant
Location: chr10:102416434 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 56.76
Residue 202: the 'disordered' region

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-arg202his (accessed [today's date]).

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