Is CHCHD10 p.Pro38Ser (c.112C>T) pathogenic?

CHCHD10 p.Pro38Ser (c.112C>T) is classified Uncertain significance in CHCHD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-20). AlphaMissense: likely benign (0.0511); Very rare (popmax 0.000268%, nfe).

How common is CHCHD10 p.Pro38Ser (c.112C>T) in the general population?

CHCHD10 p.Pro38Ser (c.112C>T) is very rare (popmax 0.000268%, nfe) (gnomAD).

What do computational predictors say about CHCHD10 p.Pro38Ser (c.112C>T)?

AlphaMissense predicts likely benign (score 0.0511) — an in-silico prediction, not a clinical call.

CHCHD10 p.Pro38Ser

c.112C>T · VCV4947147

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0511 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000268%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0511	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -7.64	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 -0.14	GERP -4.2
Regional constraint	o/e 1.03	unconstrained · MANE · 1,864 bp · p 0.66 · regional, not allelic
Overall
CADD	14.71	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 0.000268% European (non-Finnish) · 3/1,119,298 alleles

Filtering AF 7.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000224% 3/1,338,042 alleles · very rare

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: CHCHD10
Protein: p.Pro38Ser
Coding: c.112C>T
MANE Select: NM_213720
Type: single nucleotide variant
Location: chr22:23767523 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.01 · 5 PDB
Residue 38: the 'disordered' region

Full CHCHD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHCHD10 p.Pro38Leu Likely benign ★★ ⚠ same residue
CHCHD10 p.Pro38= Likely benign ★ same residue
CHCHD10 p.Ser59Leu Pathogenic/Likely pathogenic ★★ same type
CHCHD10 c.262-3C>G Uncertain significance ★★ same type
CHCHD10 c.409+1G>A Uncertain significance ★★ same type
CHCHD10 p.Ala31Val Uncertain significance ★★ ⚠ same type
CHCHD10 p.Ala35Thr Uncertain significance ★★ ⚠ same type
CHCHD10 p.Ala49Val Uncertain significance ★★ ⚠ same type

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/chchd10-p-pro38ser (accessed [today's date]).

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