Is VEGFA p.Ser344= (c.1032C>T) pathogenic?

VEGFA p.Ser344= (c.1032C>T) is classified Likely benign in VEGFA (ClinVar, Single submitter, 2 submitters; last evaluated 2018-02-02). Ultra-rare (popmax 0.0167%, amr).

How common is VEGFA p.Ser344= (c.1032C>T) in the general population?

VEGFA p.Ser344= (c.1032C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

VEGFA p.Ser344=

c.1032C>T · rs777846438 · VCV723286

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.047	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.9	GERP 1.2, phastCons 1
Overall
CADD	17.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/59,988 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.0026% 42/1,613,858 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,999
African / African-American	0.00668%	14,971
Remaining individualsnot grpmax-eligible	0.0032%	31,238
East Asian	0.00223%	44,878
South Asian	0.0022%	45,534
European (non-Finnish)	0.00186%	53,637

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: VEGFA
Protein: p.Ser344=
Coding: c.1032C>T
MANE Select: NM_003376
dbSNP: rs777846438
Type: single nucleotide variant
Location: chr6:43780801 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.19 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 65.32 · 57 PDB
Residue 344: the 'disordered' region

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

Similar variants

VEGFA p.Asn371= Likely benign ★★ same type
VEGFA c.1034+36G>C Uncertain significance ★ ⚠ same type
VEGFA c.1034+42C>T Uncertain significance ★ ⚠ same type
VEGFA p.Ala123Glu Uncertain significance ★ same type
VEGFA p.Ala133Glu Uncertain significance ★ same type
VEGFA p.Ala79Asp Uncertain significance ★ same type
VEGFA p.Arg114Pro Uncertain significance ★ same type
VEGFA p.Arg171Gly 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/vegfa-p-ser344 (accessed [today's date]).

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