Is CHTF8 p.Arg29Cys (c.85C>T) pathogenic?

CHTF8 p.Arg29Cys (c.85C>T) is classified Uncertain significance in CHTF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-30). AlphaMissense: likely benign (0.2521); Very rare (popmax 0.00879%, sas).

How common is CHTF8 p.Arg29Cys (c.85C>T) in the general population?

CHTF8 p.Arg29Cys (c.85C>T) is very rare (popmax 0.00879%, sas) (gnomAD).

What do computational predictors say about CHTF8 p.Arg29Cys (c.85C>T)?

AlphaMissense predicts likely benign (score 0.2521) — an in-silico prediction, not a clinical call.

CHTF8 p.Arg29Cys

c.85C>T · rs375808540 · VCV2330133

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2521 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00879%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2521	likely benign
REVEL	0.715	pathogenic-leaning
SaProt	LLR -10.24	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,030 bp · p 0.29 · regional, not allelic
Overall
CADD	32.0	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 0.00879% South Asian · 8/91,060 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00322% 52/1,613,736 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00879%	11,382
African / African-American	0.00401%	24,967
European (non-Finnish)	0.00314%	31,893
East Asian	0.00223%	44,878
Admixed American	0.00167%	59,996
Remaining individualsnot grpmax-eligible	0.0016%	62,458
Finnishnot grpmax-eligible	0.00156%	64,028

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: CHTF8
Protein: p.Arg29Cys
Coding: c.85C>T
MANE Select: NM_001039690
dbSNP: rs375808540
Type: single nucleotide variant
Location: chr16:69121109 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 86.99

Full CHTF8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHTF8 p.Ala28Val Uncertain significance ★ ⚠ same type
CHTF8 p.Arg109Cys Uncertain significance ★ ⚠ same type
CHTF8 p.Arg88His Uncertain significance ★ ⚠ same type
CHTF8 p.Arg88Ser Uncertain significance ★ ⚠ same type
CHTF8 p.Arg93Gln Uncertain significance ★ ⚠ same type
CHTF8 p.Arg93Trp Uncertain significance ★ ⚠ same type
CHTF8 p.Glu67Asp Uncertain significance ★ ⚠ same type
CHTF8 p.Gly33Glu 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/chtf8-p-arg29cys (accessed [today's date]).

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