Is COMMD8 p.Pro71Ser (c.211C>T) pathogenic?

COMMD8 p.Pro71Ser (c.211C>T) is classified Likely benign in COMMD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.0541); Absent from gnomAD v4.1.

How common is COMMD8 p.Pro71Ser (c.211C>T) in the general population?

COMMD8 p.Pro71Ser (c.211C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COMMD8 p.Pro71Ser (c.211C>T)?

AlphaMissense predicts likely benign (score 0.0541) — an in-silico prediction, not a clinical call.

COMMD8 p.Pro71Ser

c.211C>T · VCV4655806

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0541 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0541	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -4.18	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 1.4	GERP -1.4, phastCons 0.88
Regional constraint	o/e 1.03	unconstrained · MANE · 12 kb · p 0.69 · regional, not allelic
Overall
CADD	0.095	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: COMMD8
Protein: p.Pro71Ser
Coding: c.211C>T
MANE Select: NM_017845
Type: single nucleotide variant
Location: chr4:47460155 (GRCh38)
Gene constraint: LOEUF 1.369 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 3 PDB

Full COMMD8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD8 p.Trp122Gly Uncertain significance ★★ ⚠ same type
COMMD8 p.Arg11Gln Uncertain significance ★ ⚠ same type
COMMD8 p.Arg97Gly Uncertain significance ★ same type
COMMD8 p.Asp131Glu Uncertain significance ★ ⚠ same type
COMMD8 p.Gln116Arg Uncertain significance ★ ⚠ same type
COMMD8 p.Glu108Asp Uncertain significance ★ ⚠ same type
COMMD8 p.Glu164Gly Uncertain significance ★ ⚠ same type
COMMD8 p.Glu47Val 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/commd8-p-pro71ser (accessed [today's date]).

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