Is CD34 p.Val127Ile (c.379G>A) pathogenic?

CD34 p.Val127Ile (c.379G>A) is classified Likely benign in CD34 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-26). AlphaMissense: likely benign (0.0634); Rare (popmax 0.234%, nfe).

How common is CD34 p.Val127Ile (c.379G>A) in the general population?

CD34 p.Val127Ile (c.379G>A) is rare (popmax 0.234%, nfe) (gnomAD).

What do computational predictors say about CD34 p.Val127Ile (c.379G>A)?

AlphaMissense predicts likely benign (score 0.0634) — an in-silico prediction, not a clinical call.

CD34 p.Val127Ile

c.379G>A · rs146237257 · VCV725461

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0634 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.234%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0634	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -6.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -3.4
Regional constraint	o/e 0.91	unconstrained · MANE · 23 kb · p 0.059 · regional, not allelic
Overall
CADD	0.007	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 0.234% European (non-Finnish) · 2,757/1,180,028 alleles

Filtering AF 0.226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.223%

Overall 0.182% 2,940/1,614,158 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.234%	428
Remaining individualsnot grpmax-eligible	0.122%	823
Middle Eastern	0.066%	1,515
African / African-American	0.0426%	2,345
South Asian	0.0384%	2,602
East Asian	0.0334%	2,992
Admixed American	0.0233%	4,288
Finnishnot grpmax-eligible	0.0109%	9,145

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.Val127Ile
Coding: c.379G>A
MANE Select: NM_001025109
dbSNP: rs146237257
Type: single nucleotide variant
Location: chr1:207899110 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99
Residue 127: the 'disordered' region

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

Similar variants

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
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-val127ile (accessed [today's date]).

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