Is COMMD1 p.Thr80Ile (c.239C>T) pathogenic?

COMMD1 p.Thr80Ile (c.239C>T) is classified Uncertain significance in COMMD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-05). AlphaMissense: ambiguous (0.4192); Absent from gnomAD v4.1.

How common is COMMD1 p.Thr80Ile (c.239C>T) in the general population?

COMMD1 p.Thr80Ile (c.239C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COMMD1 p.Thr80Ile (c.239C>T)?

AlphaMissense predicts ambiguous (score 0.4192) — an in-silico prediction, not a clinical call.

COMMD1 p.Thr80Ile

c.239C>T · VCV4005676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4192 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4192	ambiguous
REVEL	0.177	moderately benign-leaning
SaProt	LLR -8.87	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 230 kb · p 0.012 · regional, not allelic
Overall
CADD	21.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COMMD1
Protein: p.Thr80Ile
Coding: c.239C>T
MANE Select: NM_152516
Type: single nucleotide variant
Location: chr2:62000759 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.58 · 4 PDB
Residue 80: an α-helix; the 'sufficient for interaction with slc12a2' region

Full COMMD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD1 p.Asn111Ile Uncertain significance ★ ⚠ same type
COMMD1 p.Asn190Asp Uncertain significance ★ ⚠ same type
COMMD1 p.Gln131His Uncertain significance ★ ⚠ same type
COMMD1 p.Gln137Glu Uncertain significance ★ ⚠ same type
COMMD1 p.Glu148Asp Uncertain significance ★ ⚠ same type
COMMD1 p.Glu33Val Uncertain significance ★ ⚠ same type
COMMD1 p.Glu5Asp Uncertain significance ★ ⚠ same type
COMMD1 p.Gly121Asp 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/commd1-p-thr80ile (accessed [today's date]).

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