Is FLG p.Pro660Arg (c.1979C>G) pathogenic?

FLG p.Pro660Arg (c.1979C>G) is classified Uncertain significance in FLG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-25). AlphaMissense: likely benign (0.096); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with FLG p.Pro660Arg (c.1979C>G)?

FLG p.Pro660Arg (c.1979C>G) is associated with Inborn genetic diseases (ClinVar).

How common is FLG p.Pro660Arg (c.1979C>G) in the general population?

FLG p.Pro660Arg (c.1979C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about FLG p.Pro660Arg (c.1979C>G)?

AlphaMissense predicts likely benign (score 0.096) — an in-silico prediction, not a clinical call.

FLG p.Pro660Arg

c.1979C>G · rs775331217 · VCV2512068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.096 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.096	likely benign
REVEL	0.014	strongly 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 -2.2	GERP -2.5
Overall
CADD	0.551	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 0.0011% South Asian · 1/91,072 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,613,878 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,072
European (non-Finnish)	0.000593%	168,575

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.Pro660Arg
Coding: c.1979C>G
dbSNP: rs775331217
Type: single nucleotide variant
Location: chr1:152312907 (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-pro660arg (accessed [today's date]).

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