Is CHTF8 p.Arg88Ser (c.262C>A) pathogenic?

CHTF8 p.Arg88Ser (c.262C>A) is classified Uncertain significance in CHTF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.1059); Absent from gnomAD v4.1.

How common is CHTF8 p.Arg88Ser (c.262C>A) in the general population?

CHTF8 p.Arg88Ser (c.262C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHTF8 p.Arg88Ser (c.262C>A)?

AlphaMissense predicts likely benign (score 0.1059) — an in-silico prediction, not a clinical call.

CHTF8 p.Arg88Ser

c.262C>A · rs375674216 · VCV2211031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1059 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1059	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -4.87	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 0.47	GERP -4.8, phastCons 0.006
Regional constraint	o/e 0.91	unconstrained · MANE · 1,030 bp · p 0.29 · regional, not allelic
Overall
CADD	0.612	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHTF8
Protein: p.Arg88Ser
Coding: c.262C>A
MANE Select: NM_001039690
dbSNP: rs375674216
Type: single nucleotide variant
Location: chr16:69120529 (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.Arg88His 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.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-arg88ser (accessed [today's date]).

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