Is CSTF1 p.Arg71His (c.212G>A) pathogenic?

CSTF1 p.Arg71His (c.212G>A) is classified Uncertain significance in CSTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-05). AlphaMissense: ambiguous (0.3999); Very rare (popmax 0.00223%, eas).

How common is CSTF1 p.Arg71His (c.212G>A) in the general population?

CSTF1 p.Arg71His (c.212G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CSTF1 p.Arg71His (c.212G>A)?

AlphaMissense predicts ambiguous (score 0.3999) — an in-silico prediction, not a clinical call.

CSTF1 p.Arg71His

c.212G>A · VCV4007767

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3999	ambiguous
REVEL	0.249	benign-leaning
SaProt	LLR -6.57	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.8	GERP 2.8, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 1,983 bp · p 1.6e-11 · regional, not allelic
Overall
CADD	24.0	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 0.00223% East Asian · 1/44,898 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000496% 8/1,614,026 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,898
Admixed American	0.00167%	60,000
European (non-Finnish)	0.000508%	196,671

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: CSTF1
Protein: p.Arg71His
Coding: c.212G>A
MANE Select: NM_001324
Type: single nucleotide variant
Location: chr20:56397249 (GRCh38)
Gene constraint: LOEUF 0.116 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.65 · 2 PDB

Full CSTF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSTF1 p.Ala68Val Uncertain significance ★ ⚠ same type
CSTF1 p.Arg11His Uncertain significance ★ ⚠ same type
CSTF1 p.Arg221Cys Uncertain significance ★ ⚠ same type
CSTF1 p.Arg339Gln Uncertain significance ★ ⚠ same type
CSTF1 p.Arg401Cys Uncertain significance ★ ⚠ same type
CSTF1 p.Asn32Ser Uncertain significance ★ ⚠ same type
CSTF1 p.Asn36Ser Uncertain significance ★ ⚠ same type
CSTF1 p.Asp290Asn 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/cstf1-p-arg71his (accessed [today's date]).

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