Is CHM p.Arg555Thr (c.1664G>C) pathogenic?

CHM p.Arg555Thr (c.1664G>C) is classified Uncertain significance in CHM (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-06-08). AlphaMissense: ambiguous (0.5545); Ultra-rare (popmax 0.0104%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHM p.Arg555Thr (c.1664G>C)?

CHM p.Arg555Thr (c.1664G>C) is associated with Inborn genetic diseases, choroideremia (ClinVar).

How common is CHM p.Arg555Thr (c.1664G>C) in the general population?

CHM p.Arg555Thr (c.1664G>C) is ultra-rare (popmax 0.0104%, nfe) (gnomAD).

What do computational predictors say about CHM p.Arg555Thr (c.1664G>C)?

AlphaMissense predicts ambiguous (score 0.5545) — an in-silico prediction, not a clinical call.

CHM p.Arg555Thr

c.1664G>C · rs143212912 · VCV947713

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.5545 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0104%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5545	ambiguous
REVEL	0.629	indeterminate
SaProt	LLR -10.42	damaging
Splicing
SpliceAI	Δ0.22	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.3	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	23.7	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

Grpmax group 0.0104% European (non-Finnish) · 93/891,229 alleles

Filtering AF 0.00868% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00805%

Overall 0.00897% 98/1,092,098 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0104%	9,583
Remaining individualsnot grpmax-eligible	0.00844%	11,853
African / African-American	0.00173%	57,696

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.Arg555Thr
Coding: c.1664G>C
MANE Select: NM_000390
dbSNP: rs143212912
Type: single nucleotide variant
Location: chrX:85873158 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: choroideremia

Similar variants

CHM p.Arg555Ter Pathogenic ★★ same residue
CHM c.116+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHM c.116+1G>T Pathogenic/Likely pathogenic ★★ same condition
CHM c.1166+1G>A Pathogenic ★★ same condition
CHM c.1166+1G>C Pathogenic ★★ same condition
CHM c.1350-1G>A Pathogenic/Likely pathogenic ★★ same condition
CHM c.1413+1G>T Pathogenic ★★ same condition
CHM c.1511-1G>A 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-arg555thr (accessed [today's date]).

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