Is VIL1 p.Phe802Ser (c.2405T>C) pathogenic?

VIL1 p.Phe802Ser (c.2405T>C) is classified Uncertain significance in VIL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely pathogenic (0.5977); Very rare (popmax 0.00667%, amr).

How common is VIL1 p.Phe802Ser (c.2405T>C) in the general population?

VIL1 p.Phe802Ser (c.2405T>C) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about VIL1 p.Phe802Ser (c.2405T>C)?

AlphaMissense predicts likely pathogenic (score 0.5977) — an in-silico prediction, not a clinical call.

VIL1 p.Phe802Ser

c.2405T>C · rs767343909 · VCV2329905

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5977 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5977	likely pathogenic
REVEL	0.362	indeterminate
SaProt	LLR -14.14	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 26 kb · p 0.0007 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00667% Admixed American · 4/60,000 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00409% 66/1,613,906 alleles · very rare exomes 64/1,461,750 · genomes 2/152,156 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0109%	9,145
Admixed Americangrpmax	0.00667%	15,000
European (non-Finnish)	0.00441%	22,691
African / African-American	0.00267%	37,450
Remaining individualsnot grpmax-eligible	0.0016%	62,482

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: VIL1
Protein: p.Phe802Ser
Coding: c.2405T>C
MANE Select: NM_007127
dbSNP: rs767343909
Type: single nucleotide variant
Location: chr2:218449257 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.98 · 2 PDB
Residue 802: the 'headpiece' region; a turn; the hp domain

Full VIL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VIL1 p.Arg505Gln Uncertain significance ★★ ⚠ same type
VIL1 p.Ala673= Benign ★★ same type
VIL1 p.Arg630Cys Benign ★★ same type
VIL1 p.Asn593Lys Benign ★★ same type
VIL1 p.His228Gln Likely benign ★★ same type
VIL1 p.Val258Leu Benign ★★ same type
VIL1 p.Ala123Val Uncertain significance ★ ⚠ same type
VIL1 p.Ala218Ser 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/vil1-p-phe802ser (accessed [today's date]).

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