Is FLG p.His770Pro (c.2309A>C) pathogenic?

FLG p.His770Pro (c.2309A>C) is classified Likely benign in FLG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0481); Very rare (popmax 0.00992%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FLG p.His770Pro (c.2309A>C)?

FLG p.His770Pro (c.2309A>C) is associated with Inborn genetic diseases (ClinVar).

How common is FLG p.His770Pro (c.2309A>C) in the general population?

FLG p.His770Pro (c.2309A>C) is very rare (popmax 0.00992%, nfe) (gnomAD).

What do computational predictors say about FLG p.His770Pro (c.2309A>C)?

AlphaMissense predicts likely benign (score 0.0481) — an in-silico prediction, not a clinical call.

FLG p.His770Pro

c.2309A>C · VCV4257952

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0481 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00992%, 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	0.0481	likely benign
REVEL	0.025	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 -4.5	GERP -2.9
Regional constraint	o/e 1.77	unconstrained · MANE · 8,404 bp · p 0 · regional, not allelic
Overall
CADD	0.314	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 0.00992% European (non-Finnish) · 117/1,179,918 alleles

Filtering AF 0.00843% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00787%

Overall 0.00769% 124/1,613,464 alleles · very rare exomes 118/1,461,864 · genomes 6/151,600 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00992%	10,085
Finnishnot grpmax-eligible	0.00312%	32,007
African / African-American	0.00268%	37,325
South Asian	0.0022%	45,519
Admixed American	0.00167%	59,952

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.His770Pro
Coding: c.2309A>C
MANE Select: NM_002016
Type: single nucleotide variant
Location: chr1:152312577 (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-his770pro (accessed [today's date]).

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