Is CHTF18 p.Pro341Ser (c.1021C>T) pathogenic?

CHTF18 p.Pro341Ser (c.1021C>T) is classified Likely benign in CHTF18 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0632); Ultra-rare (popmax 0.0294%, afr).

How common is CHTF18 p.Pro341Ser (c.1021C>T) in the general population?

CHTF18 p.Pro341Ser (c.1021C>T) is ultra-rare (popmax 0.0294%, afr) (gnomAD).

What do computational predictors say about CHTF18 p.Pro341Ser (c.1021C>T)?

AlphaMissense predicts likely benign (score 0.0632) — an in-silico prediction, not a clinical call.

CHTF18 p.Pro341Ser

c.1021C>T · VCV4653725

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0632 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0294%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0632	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -6.14	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 -0.36	GERP -3.7
Regional constraint	o/e 1.43	unconstrained · MANE · 9,287 bp · p 1.1e-58 · regional, not allelic
Overall
CADD	0.184	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 0.0294% African / African-American · 22/74,928 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00205% 33/1,610,764 alleles · ultra-rare exomes 16/1,458,512 · genomes 17/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0294%	3,406
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,548
Admixed American	0.00334%	29,960
Remaining individualsnot grpmax-eligible	0.00321%	31,186
European (non-Finnish)	0.000509%	196,594

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: CHTF18
Protein: p.Pro341Ser
Coding: c.1021C>T
MANE Select: NM_022092
Type: single nucleotide variant
Location: chr16:791287 (GRCh38)
Gene constraint: LOEUF 1.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.97 · 10 PDB
Residue 341: the 'disordered' region

Full CHTF18 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHTF18 p.Ala770= Benign ★★ same type
CHTF18 p.Arg804Cys Benign ★★ same type
CHTF18 p.Asn820= Benign ★★ same type
CHTF18 p.Asp284Glu Benign ★★ same type
CHTF18 p.Glu233Lys Benign ★★ same type
CHTF18 p.His179= Benign ★★ same type
CHTF18 p.Leu541= Benign ★★ same type
CHTF18 p.Leu797= Benign ★★ 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/chtf18-p-pro341ser (accessed [today's date]).

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