Is CPSF7 p.Arg381His (c.1142G>A) pathogenic?

CPSF7 p.Arg381His (c.1142G>A) is classified Uncertain significance in CPSF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely benign (0.3095); Very rare (popmax 0.00133%, afr).

How common is CPSF7 p.Arg381His (c.1142G>A) in the general population?

CPSF7 p.Arg381His (c.1142G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CPSF7 p.Arg381His (c.1142G>A)?

AlphaMissense predicts likely benign (score 0.3095) — an in-silico prediction, not a clinical call.

CPSF7 p.Arg381His

c.1142G>A · VCV4006411

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3095 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3095	likely benign
REVEL	0.503	indeterminate
SaProt	LLR -10.79	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 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 18 kb · p 2.7e-11 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R390H vs ClinVar R381H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,034 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000547% 8/1,461,476 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,034
European (non-Finnish)	0.000593%	168,526

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: CPSF7
Protein: p.Arg381His
Coding: c.1142G>A
MANE Select: NM_001142565
Type: single nucleotide variant
Location: chr11:61411853 (GRCh38)
Gene constraint: LOEUF 0.13 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.55 · 1 PDB

Full CPSF7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPSF7 c.-15C>T Uncertain significance ★ same type
CPSF7 c.-21C>G Uncertain significance ★ same type
CPSF7 c.-56+117C>T Uncertain significance ★ same type
CPSF7 c.-56+123C>G Uncertain significance ★ same type
CPSF7 c.-56+124C>T Uncertain significance ★ same type
CPSF7 c.-56+133G>C Uncertain significance ★ same type
CPSF7 c.-56+138G>C Uncertain significance ★ same type
CPSF7 c.-56+150C>T 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/cpsf7-p-arg381his (accessed [today's date]).

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