Is CHM p.Pro73Ser (c.217C>T) pathogenic?

CHM p.Pro73Ser (c.217C>T) is classified Likely benign in CHM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-12). AlphaMissense: likely benign (0.0635); Ultra-rare (popmax 0.0227%, afr); Associated with Inborn genetic diseases.

What condition is associated with CHM p.Pro73Ser (c.217C>T)?

CHM p.Pro73Ser (c.217C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHM p.Pro73Ser (c.217C>T) in the general population?

CHM p.Pro73Ser (c.217C>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about CHM p.Pro73Ser (c.217C>T)?

AlphaMissense predicts likely benign (score 0.0635) — an in-silico prediction, not a clinical call.

CHM p.Pro73Ser

c.217C>T · rs775421659 · VCV1095317

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0635 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0635	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -4.69	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 -0.15	GERP -3.5
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	2.805	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 0.0227% African / African-American · 13/57,151 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00207% 25/1,204,827 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,396
Admixed American	0.0197%	5,072
Remaining individualsnot grpmax-eligible	0.00634%	15,773

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.Pro73Ser
Coding: c.217C>T
MANE Select: NM_000390
dbSNP: rs775421659
Type: single nucleotide variant
Location: chrX:85978864 (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

Similar variants

CHM p.Pro73Ala Uncertain significance ★ ⚠ same residue
CHM p.Pro73Leu Uncertain significance ★ ⚠ same residue
CHM p.Ala123Val Uncertain significance ★★ ⚠ same condition
CHM p.Ala133Thr Uncertain significance ★★ ⚠ same condition
CHM p.Ala166Glu Uncertain significance ★★ ⚠ same condition
CHM p.Arg555Thr Uncertain significance ★★ ⚠ same condition
CHM p.Asn553Asp Uncertain significance ★★ ⚠ same condition
CHM p.Asn610Asp Uncertain significance ★★ ⚠ 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-pro73ser (accessed [today's date]).

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