Is CHCHD1 p.Ser50Ala (c.148T>G) pathogenic?

CHCHD1 p.Ser50Ala (c.148T>G) is classified Likely benign in CHCHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.0869); Ultra-rare (popmax 0.0646%, eas).

How common is CHCHD1 p.Ser50Ala (c.148T>G) in the general population?

CHCHD1 p.Ser50Ala (c.148T>G) is ultra-rare (popmax 0.0646%, eas) (gnomAD).

What do computational predictors say about CHCHD1 p.Ser50Ala (c.148T>G)?

AlphaMissense predicts likely benign (score 0.0869) — an in-silico prediction, not a clinical call.

CHCHD1 p.Ser50Ala

c.148T>G · rs201844542 · VCV3144056

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0869 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0646%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0869	likely benign
REVEL	0.299	indeterminate
SaProt	LLR -9.26	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.85, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 1,108 bp · p 0.7 · regional, not allelic
Overall
CADD	21.4	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 0.0646% East Asian · 29/44,884 alleles

Filtering AF 0.0461% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0399%

Overall 0.00198% 32/1,614,070 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0646%	1,548
Remaining individualsnot grpmax-eligible	0.0048%	20,833

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: CHCHD1
Protein: p.Ser50Ala
Coding: c.148T>G
MANE Select: NM_203298
dbSNP: rs201844542
Type: single nucleotide variant
Location: chr10:73782346 (GRCh38)
Gene constraint: LOEUF 1.628 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.51 · 64 PDB
Residue 50: the chch domain; a disulfide bond; an α-helix

Full CHCHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHCHD1 p.Ala83Val Uncertain significance ★ ⚠ same type
CHCHD1 p.Arg32Pro Uncertain significance ★ ⚠ same type
CHCHD1 p.Arg7Trp Uncertain significance ★ ⚠ same type
CHCHD1 p.Arg9Leu Uncertain significance ★ ⚠ same type
CHCHD1 p.Asn24Ser Uncertain significance ★ ⚠ same type
CHCHD1 p.Gln90Arg Uncertain significance ★ ⚠ same type
CHCHD1 p.Glu95Lys Uncertain significance ★ ⚠ same type
CHCHD1 p.Ile70Asn 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/chchd1-p-ser50ala (accessed [today's date]).

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