Is ARHGDIG p.Arg193Gln (c.578G>A) pathogenic?

ARHGDIG p.Arg193Gln (c.578G>A) is classified Uncertain significance in ARHGDIG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). AlphaMissense: likely benign (0.1443); Very rare (popmax 0.00676%, amr).

How common is ARHGDIG p.Arg193Gln (c.578G>A) in the general population?

ARHGDIG p.Arg193Gln (c.578G>A) is very rare (popmax 0.00676%, amr) (gnomAD).

What do computational predictors say about ARHGDIG p.Arg193Gln (c.578G>A)?

AlphaMissense predicts likely benign (score 0.1443) — an in-silico prediction, not a clinical call.

ARHGDIG p.Arg193Gln

c.578G>A · rs754881737 · VCV3128997

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1443 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00676%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1443	likely benign
REVEL	0.419	indeterminate
SaProt	LLR -10.81	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 2,130 bp · p 0.6 · regional, not allelic
Overall
CADD	28.5	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 0.00676% Admixed American · 4/59,166 alleles

Filtering AF 0.00228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000895% 13/1,451,876 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00676%	14,791
South Asian	0.00112%	89,494
European (non-Finnish)	0.000681%	146,946

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: ARHGDIG
Protein: p.Arg193Gln
Coding: c.578G>A
MANE Select: NM_001176
dbSNP: rs754881737
Type: single nucleotide variant
Location: chr16:282714 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.79

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

Similar variants

ARHGDIG p.Pro35= Benign ★★ same type
ARHGDIG p.Ala186Val Uncertain significance ★ ⚠ same type
ARHGDIG p.Ala190Val Uncertain significance ★ ⚠ same type
ARHGDIG p.Ala44Val Uncertain significance ★ ⚠ same type
ARHGDIG p.Ala50Gly Uncertain significance ★ ⚠ same type
ARHGDIG p.Ala50Val Uncertain significance ★ ⚠ same type
ARHGDIG p.Ala6Gly Uncertain significance ★ ⚠ same type
ARHGDIG p.Ala6Val 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/arhgdig-p-arg193gln (accessed [today's date]).

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