Is DISP3 p.Arg166Gln (c.497G>A) pathogenic?

DISP3 p.Arg166Gln (c.497G>A) is classified Likely benign in DISP3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-01-08). AlphaMissense: likely benign (0.0913); Rare (popmax 0.333%, eas); Associated with DISP3-related disorder.

What condition is associated with DISP3 p.Arg166Gln (c.497G>A)?

DISP3 p.Arg166Gln (c.497G>A) is associated with DISP3-related disorder (ClinVar).

How common is DISP3 p.Arg166Gln (c.497G>A) in the general population?

DISP3 p.Arg166Gln (c.497G>A) is rare (popmax 0.333%, eas) (gnomAD).

What do computational predictors say about DISP3 p.Arg166Gln (c.497G>A)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

DISP3 p.Arg166Gln

c.497G>A · rs375851130 · VCV3037937

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.333%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DISP3-related disorder

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.10	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 2.1	GERP 0.47, phastCons 0.15
Regional constraint	o/e 1.16	unconstrained · MANE · 1,081 bp · p 0.00054 · regional, not allelic
Overall
CADD	14.94	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 0.333% East Asian · 149/44,762 alleles

Filtering AF 0.289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.273%

Overall 0.0217% 349/1,606,342 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.333%	300
Remaining individualsnot grpmax-eligible	0.142%	705
South Asian	0.0885%	1,130
African / African-American	0.0214%	4,680
Admixed American	0.00843%	11,866
European (non-Finnish)	0.000935%	106,953

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: DISP3
Protein: p.Arg166Gln
Coding: c.497G>A
MANE Select: NM_020780
dbSNP: rs375851130
Type: single nucleotide variant
Location: chr1:11501489 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.84
Residue 166: the 'disordered' region

Full DISP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DISP3-related disorder

Similar variants

DISP3 c.1749+5G>A Likely benign same condition
DISP3 c.3230-4G>A Likely benign same condition
DISP3 p.Ala1000= Likely benign same condition
DISP3 p.Ala1297= Benign same condition
DISP3 p.Ala650Thr Benign same condition
DISP3 p.Arg1022His Likely benign same condition
DISP3 p.Arg294= Likely benign same condition
DISP3 p.Arg914= Likely benign same condition

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/disp3-p-arg166gln (accessed [today's date]).

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