Is DIO3 p.Arg3Ser (c.7C>A) pathogenic?

DIO3 p.Arg3Ser (c.7C>A) is classified Likely benign in DIO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-23). Absent from gnomAD v4.1.

How common is DIO3 p.Arg3Ser (c.7C>A) in the general population?

DIO3 p.Arg3Ser (c.7C>A) is absent from gnomAD v4.1 (gnomAD).

DIO3 p.Arg3Ser

c.7C>A · VCV3272086

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,138)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.019	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.44	GERP -1.2, phastCons 0.31
Regional constraint	o/e 0.90	unconstrained · MANE · 473 bp · p 0.13 · regional, not allelic
Overall
CADD	14.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,600,138). 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: DIO3
Protein: p.Arg3Ser
Coding: c.7C>A
MANE Select: NM_001362
Type: single nucleotide variant
Location: chr14:101561503 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI 0.95 (gnomAD)
Residue 3: the 'disordered' region

Full DIO3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DIO3 p.Ala155Val Uncertain significance ★ same type
DIO3 p.Ala20Thr Uncertain significance ★ same type
DIO3 p.Ala240Thr Uncertain significance ★ same type
DIO3 p.Ala40Gly Uncertain significance ★ same type
DIO3 p.Ala40Val Uncertain significance ★ same type
DIO3 p.Arg291Ser Uncertain significance ★ same type
DIO3 p.Arg300Trp Uncertain significance ★ same type
DIO3 p.Arg75Cys 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/dio3-p-arg3ser (accessed [today's date]).

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