Is CD34 p.Ser354Arg (c.1060A>C) pathogenic?

CD34 p.Ser354Arg (c.1060A>C) is classified Uncertain significance in CD34 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-30). AlphaMissense: ambiguous (0.5634); Very rare (popmax 0.00133%, afr).

How common is CD34 p.Ser354Arg (c.1060A>C) in the general population?

CD34 p.Ser354Arg (c.1060A>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CD34 p.Ser354Arg (c.1060A>C)?

AlphaMissense predicts ambiguous (score 0.5634) — an in-silico prediction, not a clinical call.

CD34 p.Ser354Arg

c.1060A>C · VCV3829539

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5634	ambiguous
REVEL	0.082	moderately benign-leaning
SaProt	LLR -6.29	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.25	GERP 1.5, phastCons 0.097
Regional constraint	o/e 0.91	unconstrained · MANE · 23 kb · p 0.059 · regional, not allelic
Overall
CADD	21.5	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 0.00133% African / African-American · 1/74,936 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.00062% 10/1,614,096 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,936
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: CD34
Protein: p.Ser354Arg
Coding: c.1060A>C
MANE Select: NM_001025109
Type: single nucleotide variant
Location: chr1:207887836 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99
Residue 354: the 'disordered' region

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

Similar variants

CD34 p.Ser354Ile Uncertain significance ★ ⚠ same residue
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

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-ser354arg (accessed [today's date]).

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