Is CHM p.Leu80Phe (c.238C>T) pathogenic?

CHM p.Leu80Phe (c.238C>T) is classified Benign/Likely benign in CHM (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0828); Low-frequency (popmax 2.8%, afr); Associated with choroideremia.

What condition is associated with CHM p.Leu80Phe (c.238C>T)?

CHM p.Leu80Phe (c.238C>T) is associated with choroideremia (ClinVar).

How common is CHM p.Leu80Phe (c.238C>T) in the general population?

CHM p.Leu80Phe (c.238C>T) is low-frequency (popmax 2.8%, afr) (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.Leu80Phe (c.238C>T)?

AlphaMissense predicts likely benign (score 0.0828) — an in-silico prediction, not a clinical call.

CHM p.Leu80Phe

c.238C>T · rs55741408 · VCV698157

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0828 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.8%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

choroideremia

Computational evidence

Protein change
AlphaMissense	0.0828	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -9.35	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 5.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	21.0	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 2.8% African / African-American · 1,602/57,213 alleles

Filtering AF 2.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.64%

Overall 0.176% 2,122/1,204,488 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.8%	36
Middle Eastern	0.415%	241
Admixed American	0.324%	309
Remaining individualsnot grpmax-eligible	0.281%	356
European (non-Finnish)	0.0234%	4,282
South Asian	0.0229%	4,360

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.Leu80Phe
Coding: c.238C>T
MANE Select: NM_000390
dbSNP: rs55741408
Type: single nucleotide variant
Location: chrX:85978843 (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-leu80phe (accessed [today's date]).

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