Is DUXA p.Ser196Pro (c.586T>C) pathogenic?

DUXA p.Ser196Pro (c.586T>C) is classified Uncertain significance in DUXA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.0788); Absent from gnomAD v4.1.

How common is DUXA p.Ser196Pro (c.586T>C) in the general population?

DUXA p.Ser196Pro (c.586T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUXA p.Ser196Pro (c.586T>C)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

DUXA p.Ser196Pro

c.586T>C · VCV4662623

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,840)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -6.94	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 0.56	GERP -2.7
Regional constraint	o/e 1.02	unconstrained · MANE · 13 kb · p 0.79 · regional, not allelic
Overall
CADD	10.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,840). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DUXA
Protein: p.Ser196Pro
Coding: c.586T>C
MANE Select: NM_001012729
Type: single nucleotide variant
Location: chr19:57154441 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.04
Residue 196: the 'disordered' region

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

Similar variants

DUXA p.Ala166Val Uncertain significance ★ ⚠ same type
DUXA p.Ala68Pro Uncertain significance ★ ⚠ same type
DUXA p.Arg103Gln Uncertain significance ★ ⚠ same type
DUXA p.Arg103Trp Uncertain significance ★ same type
DUXA p.Arg105Cys Uncertain significance ★ ⚠ same type
DUXA p.Arg16Thr Uncertain significance ★ ⚠ same type
DUXA p.Arg17Cys Uncertain significance ★ same type
DUXA p.Arg19His 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/duxa-p-ser196pro (accessed [today's date]).

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