Is CD34 p.Met260Arg (c.779T>G) pathogenic?

CD34 p.Met260Arg (c.779T>G) is classified Uncertain significance in CD34 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-07). AlphaMissense: likely pathogenic (0.8455); Very rare (popmax 0.000255%, nfe).

How common is CD34 p.Met260Arg (c.779T>G) in the general population?

CD34 p.Met260Arg (c.779T>G) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about CD34 p.Met260Arg (c.779T>G)?

AlphaMissense predicts likely pathogenic (score 0.8455) — an in-silico prediction, not a clinical call.

CD34 p.Met260Arg

c.779T>G · rs749705632 · VCV2558829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8455 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8455	likely pathogenic · top 5% in CD34
REVEL	0.23	benign-leaning
SaProt	LLR -14.55	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 23 kb · p 0.059 · regional, not allelic
Overall
CADD	26.2	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 0.000255% European (non-Finnish) · 3/1,176,830 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,610,634 alleles · very rare exomes 3/1,458,364 · genomes 0/152,270 · joint denominator

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.Met260Arg
Coding: c.779T>G
MANE Select: NM_001025109
dbSNP: rs749705632
Type: single nucleotide variant
Location: chr1:207889189 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99

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.Arg323Lys 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-met260arg (accessed [today's date]).

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