Is DEDD p.Arg124His (c.371G>A) pathogenic?

DEDD p.Arg124His (c.371G>A) is classified Uncertain significance in DEDD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). AlphaMissense: likely benign (0.0819); Ultra-rare (popmax 0.0164%, mid).

How common is DEDD p.Arg124His (c.371G>A) in the general population?

DEDD p.Arg124His (c.371G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about DEDD p.Arg124His (c.371G>A)?

AlphaMissense predicts likely benign (score 0.0819) — an in-silico prediction, not a clinical call.

DEDD p.Arg124His

c.371G>A · VCV3271430

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0819 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0819	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -6.67	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 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 1,945 bp · p 6.1e-05 · regional, not allelic
Overall
CADD	23.5	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

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000682% 11/1,613,836 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Admixed American	0.00333%	29,985
African / African-American	0.00267%	37,420
East Asian	0.00223%	44,890
Remaining individualsnot grpmax-eligible	0.0016%	62,476
South Asian	0.0011%	91,090
European (non-Finnish)	0.000254%	393,334

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: DEDD
Protein: p.Arg124His
Coding: c.371G>A
MANE Select: NM_032998
Type: single nucleotide variant
Location: chr1:161123901 (GRCh38)
Gene constraint: LOEUF 0.255 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.90

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

Similar variants

DEDD p.Arg179Cys Uncertain significance ★ ⚠ same type
DEDD p.Arg196Lys Uncertain significance ★ ⚠ same type
DEDD p.Arg200Gln Uncertain significance ★ ⚠ same type
DEDD p.Arg228Cys Uncertain significance ★ ⚠ same type
DEDD p.Arg28His Uncertain significance ★ ⚠ same type
DEDD p.Arg58Cys Uncertain significance ★ ⚠ same type
DEDD p.Arg58His Uncertain significance ★ ⚠ same type
DEDD p.Arg65His 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/dedd-p-arg124his (accessed [today's date]).

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