Is CSAD p.Arg265His (c.794G>A) pathogenic?

CSAD p.Arg265His (c.794G>A) is classified Uncertain significance in CSAD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-05). AlphaMissense: likely benign (0.0879); Ultra-rare (popmax 0.0467%, amr).

How common is CSAD p.Arg265His (c.794G>A) in the general population?

CSAD p.Arg265His (c.794G>A) is ultra-rare (popmax 0.0467%, amr) (gnomAD).

What do computational predictors say about CSAD p.Arg265His (c.794G>A)?

AlphaMissense predicts likely benign (score 0.0879) — an in-silico prediction, not a clinical call.

CSAD p.Arg265His

c.794G>A · VCV3269719

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0879 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0467%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0879	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -10.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.52	GERP -4.1
Regional constraint	o/e 0.95	unconstrained · MANE · 15 kb · p 0.2 · regional, not allelic
Overall
CADD	17.93	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 0.0467% Admixed American · 28/60,006 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0286%

Overall 0.00322% 52/1,613,972 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0467%	2,143
South Asian	0.00329%	30,361
European (non-Finnish)	0.00161%	62,106
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00133%	74,914

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: CSAD
Protein: p.Arg265His
Coding: c.794G>A
MANE Select: NM_001244705
Type: single nucleotide variant
Location: chr12:53161298 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.67 · 1 PDB
Residue 265: an α-helix

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

Similar variants

CSAD p.Ala103= Benign ★★ same type
CSAD p.Ala199= Benign ★★ same type
CSAD p.Glu50= Benign ★★ same type
CSAD c.-21C>T Uncertain significance ★ same type
CSAD c.-24G>T Uncertain significance ★ same type
CSAD c.-27C>T Uncertain significance ★ same type
CSAD c.-33C>G Uncertain significance ★ same type
CSAD c.-48A>G 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/csad-p-arg265his (accessed [today's date]).

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