Is CD320 p.Arg125Cys (c.373C>T) pathogenic?

CD320 p.Arg125Cys (c.373C>T) is classified Uncertain significance in CD320 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-02). AlphaMissense: ambiguous (0.4355); Ultra-rare (popmax 0.0165%, mid).

How common is CD320 p.Arg125Cys (c.373C>T) in the general population?

CD320 p.Arg125Cys (c.373C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CD320 p.Arg125Cys (c.373C>T)?

AlphaMissense predicts ambiguous (score 0.4355) — an in-silico prediction, not a clinical call.

CD320 p.Arg125Cys

c.373C>T · rs1381251177 · VCV2304685

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4355 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
AlphaMissense	0.4355	ambiguous
REVEL	0.304	indeterminate
SaProt	LLR -6.00	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.46 · evaluated, not missing
Pangolin	Δ0.37	gain · loss 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 1.5	GERP 0.56, phastCons 0.003
Regional constraint	o/e 1.03	unconstrained · MANE · 5,824 bp · p 0.57 · regional, not allelic
Overall
CADD	17.81	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 0.0165% Middle Eastern · 1/6,052 alleles

Filtering AF 0.00132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0011%

Overall 0.0019% 30/1,574,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,052
Remaining individualsnot grpmax-eligible	0.00328%	30,508
South Asian	0.00232%	43,030
European (non-Finnish)	0.00198%	50,452
Admixed American	0.00186%	53,712
Finnishnot grpmax-eligible	0.00163%	61,212

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: CD320
Protein: p.Arg125Cys
Coding: c.373C>T
MANE Select: NM_016579
dbSNP: rs1381251177
Type: single nucleotide variant
Location: chr19:8303984 (GRCh38)
Gene constraint: LOEUF 1.488 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.61 · 6 PDB

Full CD320 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD320 p.Arg125His Likely benign ★ same residue
CD320 p.Arg129Leu Uncertain significance ★★ ⚠ same type
CD320 p.Arg138Ser Uncertain significance ★★ ⚠ same type
CD320 p.Arg254Gln Uncertain significance ★★ ⚠ same type
CD320 p.Arg258His Uncertain significance ★★ ⚠ same type
CD320 p.Asn170Ser Uncertain significance ★★ ⚠ same type
CD320 p.Asp143Asn Uncertain significance ★★ ⚠ same type
CD320 p.Asp160Asn 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/cd320-p-arg125cys (accessed [today's date]).

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