Is FLG p.Ser805Phe (c.2414C>T) pathogenic?

FLG p.Ser805Phe (c.2414C>T) is classified Likely benign in FLG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-07-01). AlphaMissense: likely benign (0.2094); Rare (popmax 0.289%, nfe).

How common is FLG p.Ser805Phe (c.2414C>T) in the general population?

FLG p.Ser805Phe (c.2414C>T) is rare (popmax 0.289%, nfe) (gnomAD).

What do computational predictors say about FLG p.Ser805Phe (c.2414C>T)?

AlphaMissense predicts likely benign (score 0.2094) — an in-silico prediction, not a clinical call.

FLG p.Ser805Phe

c.2414C>T · rs72698904 · VCV1208753

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2094 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.289%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2094	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.5	GERP -1.8
Regional constraint	o/e 1.77	unconstrained · MANE · 8,404 bp · p 0 · regional, not allelic
Overall
CADD	11.03	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.289% European (non-Finnish) · 3,405/1,179,900 alleles

Filtering AF 0.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.277%

Overall 0.282% 4,547/1,613,622 alleles · rare exomes 4,108/1,461,782 · genomes 439/151,840 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.31%	77
European (non-Finnish)grpmax	0.289%	347
Remaining individualsnot grpmax-eligible	0.258%	388
Ashkenazi Jewishnot grpmax-eligible	0.169%	592
Admixed American	0.103%	968
African / African-American	0.0441%	2,268
South Asian	0.0011%	91,040

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: FLG
Protein: p.Ser805Phe
Coding: c.2414C>T
MANE Select: NM_002016
dbSNP: rs72698904
Type: single nucleotide variant
Location: chr1:152312472 (GRCh38)

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

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/flg-p-ser805phe (accessed [today's date]).

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