Is CHAF1A p.Arg151Gln (c.452G>A) pathogenic?

CHAF1A p.Arg151Gln (c.452G>A) is classified Uncertain significance in CHAF1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.0787); Very rare (popmax 0.00934%, afr).

How common is CHAF1A p.Arg151Gln (c.452G>A) in the general population?

CHAF1A p.Arg151Gln (c.452G>A) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about CHAF1A p.Arg151Gln (c.452G>A)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

CHAF1A p.Arg151Gln

c.452G>A · rs1022490964 · VCV3144037

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -6.20	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 -1.9	GERP -3.8
Regional constraint	o/e 1.04	unconstrained · MANE · 9,135 bp · p 0.49 · regional, not allelic
Overall
CADD	2.906	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

Grpmax group 0.00934% African / African-American · 7/74,918 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00112% 18/1,614,020 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,703
South Asian	0.0022%	45,540
European (non-Finnish)	0.000763%	131,115

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: CHAF1A
Protein: p.Arg151Gln
Coding: c.452G>A
MANE Select: NM_005483
dbSNP: rs1022490964
Type: single nucleotide variant
Location: chr19:4409251 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.06 · 11 PDB
Residue 151: the 'binds to cbx1 chromo shadow domain' region; the 'disordered' region

Full CHAF1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UBXN6 p.Arg313Leu Uncertain significance ★★ ⚠ same type
CHAF1A p.Ala70= Benign ★★ same type
CHAF1A p.Trp668Ter Pathogenic ★ same type
CHAF1A p.Ala140Gly Uncertain significance ★ ⚠ same type
CHAF1A p.Ala16Pro Uncertain significance ★ ⚠ same type
CHAF1A p.Ala193Ser Uncertain significance ★ ⚠ same type
CHAF1A p.Ala193Thr Uncertain significance ★ ⚠ same type
CHAF1A p.Ala247Pro 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/chaf1a-p-arg151gln (accessed [today's date]).

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