Is CHM p.Glu61Ala (c.182A>C) pathogenic?

CHM p.Glu61Ala (c.182A>C) is classified Uncertain significance in CHM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-21). AlphaMissense: likely benign (0.1451); Very rare (popmax 0.0041%, nfe); Associated with choroideremia.

What condition is associated with CHM p.Glu61Ala (c.182A>C)?

CHM p.Glu61Ala (c.182A>C) is associated with choroideremia (ClinVar).

How common is CHM p.Glu61Ala (c.182A>C) in the general population?

CHM p.Glu61Ala (c.182A>C) is very rare (popmax 0.0041%, nfe) (gnomAD).

How is Choroideremia inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CHM p.Glu61Ala (c.182A>C)?

AlphaMissense predicts likely benign (score 0.1451) — an in-silico prediction, not a clinical call.

CHM p.Glu61Ala

c.182A>C · rs372819339 · VCV1039645

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1451 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0041%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

choroideremia

Computational evidence

Protein change
AlphaMissense	0.1451	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -3.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0041% European (non-Finnish) · 36/879,047 alleles

Filtering AF 0.003% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00266%

Overall 0.0032% 38/1,187,370 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0041%	24,418
African / African-American	0.00357%	27,992

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.Glu61Ala
Coding: c.182A>C
MANE Select: NM_000390
dbSNP: rs372819339
Type: single nucleotide variant
Location: chrX:85981744 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Disease context

choroideremia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Choroideremia (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

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
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-glu61ala (accessed [today's date]).

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