Is MLPH p.Asn60= (c.180C>T) pathogenic?

MLPH p.Asn60= (c.180C>T) is classified Benign in MLPH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-23). Common (popmax 5.35%, sas) — too common for a highly-penetrant pathogenic allele.

MLPH p.Asn60=

Q: How common is MLPH p.Asn60= (c.180C>T) in the general population?

MLPH p.Asn60= (c.180C>T) is common (popmax 5.35%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.180C>T · rs2292878 · VCV1655837

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.35%, sas) — too common for a highly-penetrant pathogenic allele

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 -11	GERP -3.8
Overall
CADD	7.369	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.35% South Asian · 4,873/91,082 alleles

Filtering AF 5.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.17%

Overall 0.672% 10,852/1,613,750 alleles · common exomes 9,734/1,461,418 · genomes 1,118/152,332 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	5.35%	19
East Asian	3.16%	32
Admixed American	2.55%	39
Finnishnot grpmax-eligible	2.38%	42
Remaining individualsnot grpmax-eligible	0.833%	120
African / African-American	0.404%	248
Middle Eastern	0.231%	433
European (non-Finnish)	0.0571%	1,751

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: MLPH
Protein: p.Asn60=
Coding: c.180C>T
MANE Select: NM_024101
dbSNP: rs2292878
Type: single nucleotide variant
Location: chr2:237510643 (GRCh38)
Gene constraint: LOEUF 0.856 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 61.58
Residue 60: the rabbd domain

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

Similar variants

MLPH p.Arg35Gln Pathogenic/Likely pathogenic ★★ same type
MLPH p.Arg35Trp Pathogenic/Likely pathogenic ★★ same type
MLPH p.Ala236Thr Uncertain significance ★★ ⚠ same type
MLPH p.Ala520Ser Uncertain significance ★★ ⚠ same type
MLPH p.Arg375Cys Uncertain significance ★★ ⚠ same type
MLPH p.Arg507Trp Uncertain significance ★★ ⚠ same type
MLPH p.Arg518Gly Uncertain significance ★★ ⚠ same type
MLPH p.Asp194Asn Uncertain significance ★★ ⚠ same type

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/mlph-p-asn60 (accessed [today's date]).

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