Is DPT p.Arg182Cys (c.544C>T) pathogenic?

DPT p.Arg182Cys (c.544C>T) is classified Conflicting classifications of pathogenicity in DPT (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-17). AlphaMissense: likely pathogenic (0.9925); Very rare (popmax 0.00667%, amr); Associated with Progressive sensorineural hearing impairment.

What condition is associated with DPT p.Arg182Cys (c.544C>T)?

DPT p.Arg182Cys (c.544C>T) is associated with Progressive sensorineural hearing impairment (ClinVar).

How common is DPT p.Arg182Cys (c.544C>T) in the general population?

DPT p.Arg182Cys (c.544C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about DPT p.Arg182Cys (c.544C>T)?

AlphaMissense predicts likely pathogenic (score 0.9925) — an in-silico prediction, not a clinical call.

DPT p.Arg182Cys

c.544C>T · rs748718975 · VCV224834

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9925 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Progressive sensorineural hearing impairment

Computational evidence

Protein change
AlphaMissense	0.9925	likely pathogenic · top 9% in DPT
REVEL	0.849	moderately pathogenic-leaning
SaProt	LLR -15.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.21	acceptor loss · deltas
Pangolin	Δ0.23	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 7.3, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 33 kb · p 0.84 · regional, not allelic
Overall
CADD	32.0	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 0.00667% Admixed American · 4/59,962 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00273% 44/1,613,404 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,991
Remaining individualsnot grpmax-eligible	0.00641%	15,612
South Asian	0.00439%	22,755
European (non-Finnish)	0.00263%	38,052
African / African-American	0.00134%	74,878

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: DPT
Protein: p.Arg182Cys
Coding: c.544C>T
MANE Select: NM_001937
dbSNP: rs748718975
Type: single nucleotide variant
Location: chr1:168696611 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.21
Residue 182: a disulfide bond; the '2 x 53-55 aa tandem repeats' region; the '3 x 6 aa repeats of d-r-[eq]-w-[nqk]-[fy]' region

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

Disease context

Progressive sensorineural hearing impairment — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPT p.Ala58= Benign ★★ same type
DPT p.Phe130= Likely benign ★★ same type
DPT p.Ser83Ile Likely benign ★★ same type
DPT p.Tyr194= Benign ★★ same type
DPT p.Val201Ile Benign ★★ same type
DPT p.Arg126Gln Uncertain significance ★ ⚠ same type
DPT p.Arg134Cys Uncertain significance ★ ⚠ same type
DPT p.Arg134His 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/dpt-p-arg182cys (accessed [today's date]).

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