Is CHM p.Ala123Val (c.368C>T) pathogenic?

CHM p.Ala123Val (c.368C>T) is classified Uncertain significance in CHM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-13). AlphaMissense: likely benign (0.0775); Very rare (popmax 0.00291%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHM p.Ala123Val (c.368C>T)?

CHM p.Ala123Val (c.368C>T) is associated with Inborn genetic diseases, choroideremia (ClinVar).

How common is CHM p.Ala123Val (c.368C>T) in the general population?

CHM p.Ala123Val (c.368C>T) is very rare (popmax 0.00291%, nfe) (gnomAD).

What do computational predictors say about CHM p.Ala123Val (c.368C>T)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

CHM p.Ala123Val

c.368C>T · rs372532715 · VCV1038440

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00291%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -6.18	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 4.1	GERP 0.44, phastCons 0.83
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	9.626	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 0.00291% European (non-Finnish) · 26/893,881 alleles

Filtering AF 0.00202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00172%

Overall 0.0024% 29/1,206,505 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00421%	23,742
European (non-Finnish)grpmax	0.00291%	34,380
African / African-American	0.00176%	56,725

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala123Val
Coding: c.368C>T
MANE Select: NM_000390
dbSNP: rs372532715
Type: single nucleotide variant
Location: chrX:85963999 (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.Ala123= Likely benign ★ 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-ala123val (accessed [today's date]).

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