Is CHAF1B p.Ser34Phe (c.101C>T) pathogenic?

CHAF1B p.Ser34Phe (c.101C>T) is classified Uncertain significance in CHAF1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely pathogenic (0.9921); Absent from gnomAD v4.1.

How common is CHAF1B p.Ser34Phe (c.101C>T) in the general population?

CHAF1B p.Ser34Phe (c.101C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHAF1B p.Ser34Phe (c.101C>T)?

AlphaMissense predicts likely pathogenic (score 0.9921) — an in-silico prediction, not a clinical call.

CHAF1B p.Ser34Phe

c.101C>T · VCV4653221

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9921 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9921	likely pathogenic · top 7% in CHAF1B
REVEL	0.63	indeterminate
SaProt	LLR -15.51	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 27 kb · p 3.3e-14 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: CHAF1B
Protein: p.Ser34Phe
Coding: c.101C>T
MANE Select: NM_005441
Type: single nucleotide variant
Location: chr21:36386237 (GRCh38)
Gene constraint: LOEUF 0.27 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.50 · 11 PDB
Residue 34: a β-strand

Full CHAF1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHAF1B p.Leu486= Benign ★★ same type
CHAF1B p.Lys506Gln Benign ★★ same type
CHAF1B p.Pro415Leu Benign ★★ same type
CHAF1B p.Thr507Met Benign ★★ same type
MPP7 p.Ala106Thr Likely benign ★★ same type
CHAF1B p.Ala105Thr Uncertain significance ★ ⚠ same type
CHAF1B p.Ala218Val Uncertain significance ★ ⚠ same type
CHAF1B p.Ala478Val 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/chaf1b-p-ser34phe (accessed [today's date]).

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