Is CHM p.Gln471Ter (c.1411C>T) pathogenic?

CHM p.Gln471Ter (c.1411C>T) is classified Pathogenic in CHM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-17). Very rare (popmax 0.000119%, nfe); Associated with CHM-related disorders.

What condition is associated with CHM p.Gln471Ter (c.1411C>T)?

CHM p.Gln471Ter (c.1411C>T) is associated with CHM-related disorders (ClinVar).

How common is CHM p.Gln471Ter (c.1411C>T) in the general population?

CHM p.Gln471Ter (c.1411C>T) is very rare (popmax 0.000119%, nfe) (gnomAD).

CHM p.Gln471Ter

c.1411C>T · rs1926202704 · VCV865800

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000119%, nfe)

Conditions

CHM-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 15
Splicing
SpliceAI	Δ0.66	donor loss · deltas
Pangolin	Δ0.70	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.3	GERP 1.9, phastCons 1
Overall
CADD	45.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000119% European (non-Finnish) · 1/842,983 alleles

Overall 9.65e-05% 1/1,036,655 alleles · very rare

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: CHM
Protein: p.Gln471Ter
Coding: c.1411C>T
MANE Select: NM_000390
dbSNP: rs1926202704
Type: single nucleotide variant
Location: chrX:85900648 (GRCh38)
Structure: AlphaFold pLDDT 81.05
Residue 471: a UniProt-annotated variant site (in chm; may affect splicing)

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

Disease context

CHM-related disorders

Similar variants

CHM p.Gln471= Conflicting classifications of pathogenicity ★ same residue
CHM c.116+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHM c.116+1G>T Pathogenic/Likely pathogenic ★★ same condition
CHM c.1167-2A>G Pathogenic ★★ same condition
CHM c.1244+2T>A Pathogenic/Likely pathogenic ★★ same condition
CHM c.1349+1G>T Pathogenic/Likely pathogenic ★★ same condition
CHM c.1511-1G>A Pathogenic ★★ same condition
CHM c.1511-2A>T Likely pathogenic ★★ same condition

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/chm-p-gln471ter (accessed [today's date]).

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