Is FLG p.Ser2279Phe (c.6836C>T) pathogenic?

FLG p.Ser2279Phe (c.6836C>T) is classified Uncertain significance in FLG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-19). AlphaMissense: likely benign (0.299); Ultra-rare (popmax 0.0108%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FLG p.Ser2279Phe (c.6836C>T)?

FLG p.Ser2279Phe (c.6836C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FLG p.Ser2279Phe (c.6836C>T) in the general population?

FLG p.Ser2279Phe (c.6836C>T) is ultra-rare (popmax 0.0108%, nfe) (gnomAD).

What do computational predictors say about FLG p.Ser2279Phe (c.6836C>T)?

AlphaMissense predicts likely benign (score 0.299) — an in-silico prediction, not a clinical call.

FLG p.Ser2279Phe

c.6836C>T · VCV3279083

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.299 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

⚠ 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	0.299	likely benign
REVEL	0.102	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 -0.2	GERP 1.4
Regional constraint	o/e 1.77	unconstrained · MANE · 8,404 bp · p 0 · regional, not allelic
Overall
CADD	17.49	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0108% European (non-Finnish) · 127/1,180,022 alleles

Filtering AF 0.00919% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00863%

Overall 0.0392% 633/1,613,954 alleles · ultra-rare exomes 534/1,461,868 · genomes 99/152,086 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.758%	132
Remaining individualsnot grpmax-eligible	0.032%	3,124
European (non-Finnish)grpmax	0.0108%	9,292
African / African-American	0.00134%	74,898

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.Ser2279Phe
Coding: c.6836C>T
MANE Select: NM_002016
Type: single nucleotide variant
Location: chr1:152308050 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ser2279phe (accessed [today's date]).

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