Is CHTF8 p.Arg93Trp (c.277C>T) pathogenic?

CHTF8 p.Arg93Trp (c.277C>T) is classified Uncertain significance in CHTF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-02). AlphaMissense: likely benign (0.1136); Very rare (popmax 0.00878%, sas).

How common is CHTF8 p.Arg93Trp (c.277C>T) in the general population?

CHTF8 p.Arg93Trp (c.277C>T) is very rare (popmax 0.00878%, sas) (gnomAD).

What do computational predictors say about CHTF8 p.Arg93Trp (c.277C>T)?

AlphaMissense predicts likely benign (score 0.1136) — an in-silico prediction, not a clinical call.

CHTF8 p.Arg93Trp

c.277C>T · rs769216163 · VCV2331779

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1136 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1136	likely benign
REVEL	0.369	indeterminate
SaProt	LLR -11.74	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,030 bp · p 0.29 · regional, not allelic
Overall
CADD	18.22	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 0.00878% South Asian · 8/91,080 alleles

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

Overall 0.000682% 11/1,614,074 alleles · very rare exomes 11/1,461,872 · genomes 0/152,202 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,385
East Asian	0.00223%	44,872
European (non-Finnish)	0.000169%	589,998

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.Arg93Trp
Coding: c.277C>T
MANE Select: NM_001039690
dbSNP: rs769216163
Type: single nucleotide variant
Location: chr16:69120514 (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.Arg93Gln Uncertain significance ★ ⚠ same residue
CHTF8 p.Ala28Val Uncertain significance ★ ⚠ same type
CHTF8 p.Arg109Cys Uncertain significance ★ ⚠ same type
CHTF8 p.Arg29Cys Uncertain significance ★ ⚠ same type
CHTF8 p.Arg88His Uncertain significance ★ ⚠ same type
CHTF8 p.Arg88Ser 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-arg93trp (accessed [today's date]).

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