Is FLNA p.Asp871= (c.2613C>T) pathogenic?

FLNA p.Asp871= (c.2613C>T) is classified Conflicting classifications of pathogenicity in FLNA (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-15). Rare (popmax 0.35%, eas); Associated with otopalatodigital syndrome type 2.

What condition is associated with FLNA p.Asp871= (c.2613C>T)?

FLNA p.Asp871= (c.2613C>T) is associated with otopalatodigital syndrome type 2, heterotopia, periventricular, X-linked dominant, Melnick-Needles syndrome (ClinVar).

How common is FLNA p.Asp871= (c.2613C>T) in the general population?

FLNA p.Asp871= (c.2613C>T) is rare (popmax 0.35%, eas) (gnomAD).

FLNA p.Asp871=

c.2613C>T · rs188212919 · VCV211014

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.35%, eas)

Conditions

otopalatodigital syndrome type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.37	GERP -1.4
Overall
CADD	3.551	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.35% East Asian · 118/33,739 alleles

Filtering AF 0.298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.279%

Overall 0.0178% 215/1,209,800 alleles · rare exomes 206/1,097,637 · genomes 9/112,163 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.35%	286
Admixed American	0.0436%	2,294
Remaining individualsnot grpmax-eligible	0.0084%	11,905
European (non-Finnish)	0.00749%	13,360
African / African-American	0.00698%	14,322
South Asian	0.00352%	28,422

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: FLNA
Protein: p.Asp871=
Coding: c.2613C>T
MANE Select: NM_001110556
dbSNP: rs188212919
Type: single nucleotide variant
Location: chrX:154362285 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB

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

Disease context

otopalatodigital syndrome type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: heterotopia, periventricular, X-linked dominant Melnick-Needles syndrome frontometaphyseal dysplasia familial thoracic aortic aneurysm and aortic dissection

Similar variants

FLNA c.1066-1G>A Pathogenic/Likely pathogenic ★★ same condition
FLNA c.2022+1G>A Pathogenic ★★ same condition
FLNA c.4598+1G>A Pathogenic/Likely pathogenic ★★ same condition
FLNA c.5417-2A>G Likely pathogenic ★★ same condition
FLNA c.868+1G>A Likely pathogenic ★★ same condition
FLNA c.987+1G>A Likely pathogenic ★★ same condition
FLNA p.Ala1188Thr Pathogenic/Likely pathogenic ★★ same condition
FLNA p.Arg1515Ter Pathogenic ★★ same condition

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/flna-p-asp871 (accessed [today's date]).

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