Is FLT1 p.Asp1108Glu (c.3324C>G) pathogenic?

FLT1 p.Asp1108Glu (c.3324C>G) is classified Uncertain significance in FLT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely benign (0.1597); Very rare (popmax 0.00246%, nfe).

How common is FLT1 p.Asp1108Glu (c.3324C>G) in the general population?

FLT1 p.Asp1108Glu (c.3324C>G) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about FLT1 p.Asp1108Glu (c.3324C>G)?

AlphaMissense predicts likely benign (score 0.1597) — an in-silico prediction, not a clinical call.

FLT1 p.Asp1108Glu

c.3324C>G · VCV3516077

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1597 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1597	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP -0.35, phastCons 0.99
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 0.052 · regional, not allelic
Overall
CADD	11.78	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% European (non-Finnish) · 29/1,179,906 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.0018% 29/1,613,900 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: FLT1
Protein: p.Asp1108Glu
Coding: c.3324C>G
MANE Select: NM_002019
Type: single nucleotide variant
Location: chr13:28317560 (GRCh38)
Gene constraint: LOEUF 0.379 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.86 · 12 PDB
Residue 1108: an α-helix; the protein kinase domain

Full FLT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FLT1 p.Asp6Asn Benign ★★ same type
FLT1 p.Cys107= Likely benign ★★ same type
FLT1 p.Ile548Met Likely benign ★★ ⚠ same type
FLT1 p.Leu492= Benign ★★ same type
FLT1 p.Met938Val Likely benign ★★ same type
FLT1 p.Pro1068= Benign ★★ same type
FLT1 p.Pro1201Leu Likely benign ★★ same type
FLT1 p.Thr260= Benign ★★ 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/flt1-p-asp1108glu (accessed [today's date]).

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