Is FLG p.Ser3606Phe (c.10817C>T) pathogenic?

FLG p.Ser3606Phe (c.10817C>T) is classified Conflicting classifications of pathogenicity in FLG (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.2152); Rare (popmax 0.119%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FLG p.Ser3606Phe (c.10817C>T)?

FLG p.Ser3606Phe (c.10817C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FLG p.Ser3606Phe (c.10817C>T) in the general population?

FLG p.Ser3606Phe (c.10817C>T) is rare (popmax 0.119%, nfe) (gnomAD).

What do computational predictors say about FLG p.Ser3606Phe (c.10817C>T)?

AlphaMissense predicts likely benign (score 0.2152) — an in-silico prediction, not a clinical call.

FLG p.Ser3606Phe

c.10817C>T · rs141368651 · VCV2366777

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2152 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.119%, 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	0.2152	likely benign
REVEL	0.038	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 -0.48	GERP -1.8
Regional constraint	o/e 1.38	unconstrained · MANE · 2,903 bp · p 2.8e-40 · regional, not allelic
Overall
CADD	16.88	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 0.119% European (non-Finnish) · 1,409/1,179,936 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.112%

Overall 0.0944% 1,523/1,612,702 alleles · rare exomes 1,425/1,461,892 · genomes 98/150,810 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.119%	837
Remaining individualsnot grpmax-eligible	0.0864%	1,157
Middle Eastern	0.0658%	1,520
Admixed American	0.0402%	2,487
African / African-American	0.0241%	4,146
Finnishnot grpmax-eligible	0.0172%	5,812
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
South Asian	0.0022%	45,448

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.Ser3606Phe
Coding: c.10817C>T
MANE Select: NM_002016
dbSNP: rs141368651
Type: single nucleotide variant
Location: chr1:152304069 (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-ser3606phe (accessed [today's date]).

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