Is CD34 p.Arg323Lys (c.968G>A) pathogenic?

CD34 p.Arg323Lys (c.968G>A) is classified Uncertain significance in CD34 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-14). AlphaMissense: ambiguous (0.3859); Very rare (popmax 0.00833%, amr).

How common is CD34 p.Arg323Lys (c.968G>A) in the general population?

CD34 p.Arg323Lys (c.968G>A) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about CD34 p.Arg323Lys (c.968G>A)?

AlphaMissense predicts ambiguous (score 0.3859) — an in-silico prediction, not a clinical call.

CD34 p.Arg323Lys

c.968G>A · VCV3829540

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3859 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Computational evidence

Protein change
AlphaMissense	0.3859	ambiguous
REVEL	0.309	indeterminate
SaProt	LLR -6.09	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 4.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 23 kb · p 0.059 · regional, not allelic
Overall
CADD	27.2	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 0.00833% Admixed American · 5/60,004 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00031% 5/1,614,048 alleles · very rare

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: CD34
Protein: p.Arg323Lys
Coding: c.968G>A
MANE Select: NM_001025109
Type: single nucleotide variant
Location: chr1:207888686 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99
Residue 323: the 'disordered' region

Full CD34 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD34 p.Val127Ile Likely benign ★★ same type
CD34 p.Ala222Val Uncertain significance ★ ⚠ same type
CD34 p.Ala224Asp Uncertain significance ★ ⚠ same type
CD34 p.Ala234Thr Uncertain significance ★ ⚠ same type
CD34 p.Ala349Thr Uncertain significance ★ ⚠ same type
CD34 p.Arg314His Uncertain significance ★ ⚠ same type
CD34 p.Arg315His Uncertain significance ★ ⚠ same type
CD34 p.Asn333His 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/cd34-p-arg323lys (accessed [today's date]).

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